<?xml version="1.0" encoding="us-ascii"?>
<!-- Created by Merrill Corporation -->
<!--XBRL document created with Merrill Bridge  7.3.329.0 -->
<!--Based on XBRL 2.1-->
<!--Created on: 11/2/2017 9:04:38 PM-->
<!--Modified on: 11/2/2017 9:04:38 PM-->
<link:linkbase xsi:schemaLocation="http://www.xbrl.org/2003/linkbase http://www.xbrl.org/2003/xbrl-linkbase-2003-12-31.xsd" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:xbrldt="http://xbrl.org/2005/xbrldt">
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureSignificantAccountingPoliciesDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureSignificantAccountingPoliciesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureFairValueMeasurementsDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureFairValueMeasurementsContingentConsiderationLiabilitiesDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsContingentConsiderationLiabilitiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureFairValueMeasurementsAdditionalInformationDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsAdditionalInformationDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureMarketableSecuritiesDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureMarketableSecuritiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureIntangibleAssetsAndGoodwillDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureIntangibleAssetsAndGoodwillDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureOtherLongTermLiabilitiesNjTaxDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilitiesNjTaxDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureOtherLongTermLiabilitiesLeaseRestructureDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilitiesLeaseRestructureDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureStockholdersEquityDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureStockholdersEquityDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureStockBasedCompensationSummaryOfPlansDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationSummaryOfPlansDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureStockBasedCompensationExpenseDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationExpenseDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureStockBasedCompensationValuationDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationValuationDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureAccumulatedOtherComprehensiveIncomeDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureAccumulatedOtherComprehensiveIncomeDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureRevenueDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureRevenueDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureKolltanAcquisitionPurchasePriceDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureKolltanAcquisitionPurchasePriceDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureKolltanAcquisitionAllocationsOfAssetsAndLiabilitiesDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureKolltanAcquisitionAllocationsOfAssetsAndLiabilitiesDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <roleRef xlink:type="simple" xlink:href="cldx-20170930.xsd#DisclosureNetLossPerShareDetails" roleURI="http://www.celldextherapeutics.com/role/DisclosureNetLossPerShareDetails" xmlns="http://www.xbrl.org/2003/linkbase" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/all" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#all" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-domain" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-domain" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/domain-member" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#domain-member" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/hypercube-dimension" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#hypercube-dimension" />
  <link:arcroleRef arcroleURI="http://xbrl.org/int/dim/arcrole/dimension-default" xlink:type="simple" xlink:href="http://www.xbrl.org/2005/xbrldt-2005.xsd#dimension-default" />
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureSignificantAccountingPoliciesDetails" xlink:type="extended" xlink:title="40201 - Disclosure - Significant Accounting Policies - (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:label="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:label="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="us-gaap_TypeOfAdoptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_TypeOfAdoptionMember" xlink:label="us-gaap_TypeOfAdoptionMember_636452534766832999" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_AdjustmentsForNewAccountingPronouncementsAxis" xlink:to="us-gaap_TypeOfAdoptionMember_636452534766832999" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AccountingStandardsUpdateMember" xlink:label="cldx_AccountingStandardsUpdateMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TypeOfAdoptionMember" xlink:to="cldx_AccountingStandardsUpdateMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NewAccountingPronouncementEarlyAdoptionAxis" xlink:label="us-gaap_NewAccountingPronouncementEarlyAdoptionAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" xlink:to="us-gaap_NewAccountingPronouncementEarlyAdoptionAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NewAccountingPrinciplesEarlyAdoptionMember" xlink:label="us-gaap_NewAccountingPrinciplesEarlyAdoptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_NewAccountingPronouncementEarlyAdoptionAxis" xlink:to="us-gaap_NewAccountingPrinciplesEarlyAdoptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NewAccountingPrinciplesEarlyAdoptionMember" xlink:label="us-gaap_NewAccountingPrinciplesEarlyAdoptionMember_636452534766843000" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_NewAccountingPronouncementEarlyAdoptionAxis" xlink:to="us-gaap_NewAccountingPrinciplesEarlyAdoptionMember_636452534766843000" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AdjustmentsForNewAccountingPrincipleEarlyAdoptionMember" xlink:label="us-gaap_AdjustmentsForNewAccountingPrincipleEarlyAdoptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_NewAccountingPrinciplesEarlyAdoptionMember" xlink:to="us-gaap_AdjustmentsForNewAccountingPrincipleEarlyAdoptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:label="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_GrossDeferredTaxAssetsAndCorrespondingValuation" xlink:label="cldx_GrossDeferredTaxAssetsAndCorrespondingValuation" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_NewAccountingPronouncementsOrChangeInAccountingPrincipleLineItems" xlink:to="cldx_GrossDeferredTaxAssetsAndCorrespondingValuation" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsDetails" xlink:type="extended" xlink:title="40301 - Disclosure - Fair Value Measurements (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueByMeasurementFrequencyAxis" xlink:label="us-gaap_FairValueByMeasurementFrequencyAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByMeasurementFrequencyAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementFrequencyDomain" xlink:label="us-gaap_FairValueMeasurementFrequencyDomain_636452534766853001" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_FairValueByMeasurementFrequencyAxis" xlink:to="us-gaap_FairValueMeasurementFrequencyDomain_636452534766853001" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementsRecurringMember" xlink:label="us-gaap_FairValueMeasurementsRecurringMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementFrequencyDomain" xlink:to="us-gaap_FairValueMeasurementsRecurringMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueByMeasurementBasisAxis" xlink:label="us-gaap_FairValueByMeasurementBasisAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByMeasurementBasisAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:label="us-gaap_PortionAtFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByMeasurementBasisAxis" xlink:to="us-gaap_PortionAtFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:label="us-gaap_PortionAtFairValueFairValueDisclosureMember_636452534766853001" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_FairValueByMeasurementBasisAxis" xlink:to="us-gaap_PortionAtFairValueFairValueDisclosureMember_636452534766853001" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EstimateOfFairValueFairValueDisclosureMember" xlink:label="us-gaap_EstimateOfFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:to="us-gaap_EstimateOfFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_636452534766863002" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain_636452534766863002" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueInputsLevel2Member" xlink:label="us-gaap_FairValueInputsLevel2Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel2Member" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AssetsFairValueDisclosureAbstract" xlink:label="us-gaap_AssetsFairValueDisclosureAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_AssetsFairValueDisclosureAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CashAndCashEquivalentsFairValueDisclosure" xlink:label="us-gaap_CashAndCashEquivalentsFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AssetsFairValueDisclosureAbstract" xlink:to="us-gaap_CashAndCashEquivalentsFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecurities" xlink:label="us-gaap_AvailableForSaleSecurities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AssetsFairValueDisclosureAbstract" xlink:to="us-gaap_AvailableForSaleSecurities" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AssetsFairValueDisclosure" xlink:label="us-gaap_AssetsFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AssetsFairValueDisclosureAbstract" xlink:to="us-gaap_AssetsFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LiabilitiesFairValueDisclosureAbstract" xlink:label="us-gaap_LiabilitiesFairValueDisclosureAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_LiabilitiesFairValueDisclosureAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContingentConsiderationClassifiedAsEquityFairValueDisclosure" xlink:label="us-gaap_ContingentConsiderationClassifiedAsEquityFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_LiabilitiesFairValueDisclosureAbstract" xlink:to="us-gaap_ContingentConsiderationClassifiedAsEquityFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LiabilitiesFairValueDisclosure" xlink:label="us-gaap_LiabilitiesFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_LiabilitiesFairValueDisclosureAbstract" xlink:to="us-gaap_LiabilitiesFairValueDisclosure" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsContingentConsiderationLiabilitiesDetails" xlink:type="extended" xlink:title="40302 - Disclosure - Fair Value Measurements - Contingent Consideration Liabilities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueByMeasurementBasisAxis" xlink:label="us-gaap_FairValueByMeasurementBasisAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByMeasurementBasisAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:label="us-gaap_PortionAtFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByMeasurementBasisAxis" xlink:to="us-gaap_PortionAtFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EstimateOfFairValueFairValueDisclosureMember" xlink:label="us-gaap_EstimateOfFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:to="us-gaap_EstimateOfFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:label="us-gaap_FairValueByFairValueHierarchyLevelAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByFairValueHierarchyLevelAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:label="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByFairValueHierarchyLevelAxis" xlink:to="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueInputsLevel3Member" xlink:label="us-gaap_FairValueInputsLevel3Member" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueMeasurementsFairValueHierarchyDomain" xlink:to="us-gaap_FairValueInputsLevel3Member" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BalanceSheetLocationAxis" xlink:label="us-gaap_BalanceSheetLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_BalanceSheetLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_BalanceSheetLocationAxis" xlink:to="us-gaap_BalanceSheetLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BalanceSheetLocationDomain" xlink:label="us-gaap_BalanceSheetLocationDomain_636452534766893005" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_BalanceSheetLocationAxis" xlink:to="us-gaap_BalanceSheetLocationDomain_636452534766893005" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_OtherNoncurrentLiabilitiesMember" xlink:label="us-gaap_OtherNoncurrentLiabilitiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BalanceSheetLocationDomain" xlink:to="us-gaap_OtherNoncurrentLiabilitiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward" xlink:label="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContingentConsiderationClassifiedAsEquityFairValueDisclosure" xlink:label="us-gaap_ContingentConsiderationClassifiedAsEquityFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward" xlink:to="us-gaap_ContingentConsiderationClassifiedAsEquityFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueLiabilitiesMeasuredOnRecurringBasisUnobservableInputReconciliationCalculationRollForward" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsAdditionalInformationDetails" xlink:type="extended" xlink:title="40303 - Disclosure - Fair Value Measurements - Additional information (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueByMeasurementBasisAxis" xlink:label="us-gaap_FairValueByMeasurementBasisAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_FairValueByMeasurementBasisAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:label="us-gaap_PortionAtFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FairValueByMeasurementBasisAxis" xlink:to="us-gaap_PortionAtFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EstimateOfFairValueFairValueDisclosureMember" xlink:label="us-gaap_EstimateOfFairValueFairValueDisclosureMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_PortionAtFairValueFairValueDisclosureMember" xlink:to="us-gaap_EstimateOfFairValueFairValueDisclosureMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_BusinessAcquisitionAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain_636452534766913007" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain_636452534766913007" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_KolltanPharmaceuticalsMember" xlink:label="cldx_KolltanPharmaceuticalsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="cldx_KolltanPharmaceuticalsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContingentConsiderationByTypeAxis" xlink:label="us-gaap_ContingentConsiderationByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" xlink:to="us-gaap_ContingentConsiderationByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:label="us-gaap_ContingentConsiderationTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:label="us-gaap_ContingentConsiderationTypeDomain_636452534766913007" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain_636452534766913007" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_ContingentMilestoneMember" xlink:label="cldx_ContingentMilestoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="cldx_ContingentMilestoneMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:label="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsChangeInAmountOfContingentConsiderationLiability1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsLevel1ToLevel2TransfersAmount" xlink:label="us-gaap_FairValueAssetsLevel1ToLevel2TransfersAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsLevel1ToLevel2TransfersAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueAssetsLevel2ToLevel1TransfersAmount" xlink:label="us-gaap_FairValueAssetsLevel2ToLevel1TransfersAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueAssetsLevel2ToLevel1TransfersAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueLiabilitiesLevel1ToLevel2TransfersAmount" xlink:label="us-gaap_FairValueLiabilitiesLevel1ToLevel2TransfersAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueLiabilitiesLevel1ToLevel2TransfersAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueLiabilitiesLevel2ToLevel1TransfersAmount" xlink:label="us-gaap_FairValueLiabilitiesLevel2ToLevel1TransfersAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueLiabilitiesLevel2ToLevel1TransfersAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetTransfersOutOfLevel3" xlink:label="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetTransfersOutOfLevel3" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetTransfersOutOfLevel3" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetTransfersIntoLevel3" xlink:label="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetTransfersIntoLevel3" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationRecurringBasisAssetTransfersIntoLevel3" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationLiabilityTransfersOutOfLevel3" xlink:label="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationLiabilityTransfersOutOfLevel3" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="10" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationLiabilityTransfersOutOfLevel3" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationLiabilityTransfersIntoLevel3" xlink:label="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationLiabilityTransfersIntoLevel3" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="11" xlink:from="us-gaap_FairValueAssetsAndLiabilitiesMeasuredOnRecurringAndNonrecurringBasisLineItems" xlink:to="us-gaap_FairValueMeasurementWithUnobservableInputsReconciliationLiabilityTransfersIntoLevel3" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureMarketableSecuritiesDetails" xlink:type="extended" xlink:title="40401 - Disclosure - Marketable Securities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesTable" xlink:label="us-gaap_ScheduleOfAvailableForSaleSecuritiesTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_MajorTypesOfDebtAndEquitySecuritiesAxis" xlink:label="us-gaap_MajorTypesOfDebtAndEquitySecuritiesAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesTable" xlink:to="us-gaap_MajorTypesOfDebtAndEquitySecuritiesAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain" xlink:label="us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_MajorTypesOfDebtAndEquitySecuritiesAxis" xlink:to="us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain" xlink:label="us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain_636452534766943010" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_MajorTypesOfDebtAndEquitySecuritiesAxis" xlink:to="us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain_636452534766943010" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_USTreasuryAndGovernmentMember" xlink:label="us-gaap_USTreasuryAndGovernmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain" xlink:to="us-gaap_USTreasuryAndGovernmentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CorporateDebtSecuritiesMember" xlink:label="us-gaap_CorporateDebtSecuritiesMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_MajorTypesOfDebtAndEquitySecuritiesDomain" xlink:to="us-gaap_CorporateDebtSecuritiesMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:label="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_ScheduleOfAvailableForSaleSecuritiesTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAmortizedCostAbstract" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAmortizedCostAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAmortizedCostAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearAmortizedCost" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearAmortizedCost" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAmortizedCostAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearAmortizedCost" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsAmortizedCost" xlink:label="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsAmortizedCost" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAmortizedCostAbstract" xlink:to="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsAmortizedCost" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" xlink:label="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesAmortizedCostAbstract" xlink:to="us-gaap_AvailableForSaleDebtSecuritiesAmortizedCostBasis" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGainAbstract" xlink:label="us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGainAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGainAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedGain" xlink:label="cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedGain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGainAbstract" xlink:to="cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedGain" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsGrossUnrealizedGain" xlink:label="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsGrossUnrealizedGain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGainAbstract" xlink:to="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsGrossUnrealizedGain" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" xlink:label="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AvailableForSaleSecuritiesGrossUnrealizedGainAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedGainBeforeTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AvailableForSaleSecuritiesGrossUnrealizedLossesAbstract" xlink:label="cldx_AvailableForSaleSecuritiesGrossUnrealizedLossesAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="cldx_AvailableForSaleSecuritiesGrossUnrealizedLossesAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedLosses" xlink:label="cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedLosses" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="cldx_AvailableForSaleSecuritiesGrossUnrealizedLossesAbstract" xlink:to="cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedLosses" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" xlink:label="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="cldx_AvailableForSaleSecuritiesGrossUnrealizedLossesAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesAccumulatedGrossUnrealizedLossBeforeTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesFairValueAbstract" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesFairValueAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesFairValueAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesFairValueAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearFairValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsFairValue" xlink:label="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesFairValueAbstract" xlink:to="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsFairValue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" xlink:label="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_AvailableForSaleSecuritiesDebtMaturitiesFairValueAbstract" xlink:to="us-gaap_AvailableForSaleSecuritiesDebtSecuritiesCurrent" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_OtherThanTemporaryImpairmentCreditLossesRecognizedInEarningsCreditLossesOnDebtSecuritiesHeld" xlink:label="us-gaap_OtherThanTemporaryImpairmentCreditLossesRecognizedInEarningsCreditLossesOnDebtSecuritiesHeld" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_OtherThanTemporaryImpairmentCreditLossesRecognizedInEarningsCreditLossesOnDebtSecuritiesHeld" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_InterestReceivable" xlink:label="us-gaap_InterestReceivable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_ScheduleOfAvailableForSaleSecuritiesLineItems" xlink:to="us-gaap_InterestReceivable" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureIntangibleAssetsAndGoodwillDetails" xlink:type="extended" xlink:title="40501 - Disclosure - Intangible Assets and Goodwill (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassTable" xlink:label="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassTable" xlink:to="us-gaap_BusinessAcquisitionAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_KolltanPharmaceuticalsMember" xlink:label="cldx_KolltanPharmaceuticalsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="cldx_KolltanPharmaceuticalsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassTable" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_636452534766993015" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain_636452534766993015" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_InProcessResearchAndDevelopmentMember" xlink:label="us-gaap_InProcessResearchAndDevelopmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_InProcessResearchAndDevelopmentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:label="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassTable" xlink:to="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:label="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_636452534766993015" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_FiniteLivedIntangibleAssetsByMajorClassAxis" xlink:to="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain_636452534766993015" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_LicensingAgreementsMember" xlink:label="us-gaap_LicensingAgreementsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FiniteLivedIntangibleAssetsMajorClassNameDomain" xlink:to="us-gaap_LicensingAgreementsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" xlink:label="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" xlink:to="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_GoodwillImpairmentLoss" xlink:label="us-gaap_GoodwillImpairmentLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" xlink:to="us-gaap_GoodwillImpairmentLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillAbstract" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillAbstract" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwill" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure" xlink:label="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillAbstract" xlink:to="us-gaap_IndefiniteLivedIntangibleAssetsExcludingGoodwillFairValueDisclosure" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetUsefulLife" xlink:label="us-gaap_FiniteLivedIntangibleAssetUsefulLife" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetUsefulLife" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsGross" xlink:label="us-gaap_FiniteLivedIntangibleAssetsGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" xlink:label="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsAccumulatedAmortization" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FiniteLivedIntangibleAssetsNet" xlink:label="us-gaap_FiniteLivedIntangibleAssetsNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_FiniteLivedIntangibleAssetsNetAbstract" xlink:to="us-gaap_FiniteLivedIntangibleAssetsNet" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwillAbstract" xlink:label="us-gaap_IntangibleAssetsNetExcludingGoodwillAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" xlink:to="us-gaap_IntangibleAssetsNetExcludingGoodwillAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IntangibleAssetsGrossExcludingGoodwill" xlink:label="us-gaap_IntangibleAssetsGrossExcludingGoodwill" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IntangibleAssetsNetExcludingGoodwillAbstract" xlink:to="us-gaap_IntangibleAssetsGrossExcludingGoodwill" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IntangibleAssetsNetExcludingGoodwill" xlink:label="us-gaap_IntangibleAssetsNetExcludingGoodwill" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IntangibleAssetsNetExcludingGoodwillAbstract" xlink:to="us-gaap_IntangibleAssetsNetExcludingGoodwill" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" xlink:label="us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="cldx_FiniteLivedAndIndefiniteLivedIntangibleAssetsByMajorClassLineItems" xlink:to="us-gaap_ImpairmentOfIntangibleAssetsIndefinitelivedExcludingGoodwill" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilitiesNjTaxDetails" xlink:type="extended" xlink:title="40602 - Disclosure - Other Long-Term Liabilities- NJ Tax (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeTaxAuthorityNameAxis" xlink:label="us-gaap_IncomeTaxAuthorityNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_IncomeTaxAuthorityNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeTaxAuthorityNameDomain" xlink:label="us-gaap_IncomeTaxAuthorityNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeTaxAuthorityNameAxis" xlink:to="us-gaap_IncomeTaxAuthorityNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeTaxAuthorityNameDomain" xlink:label="us-gaap_IncomeTaxAuthorityNameDomain_636452534767033019" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_IncomeTaxAuthorityNameAxis" xlink:to="us-gaap_IncomeTaxAuthorityNameDomain_636452534767033019" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_NewJerseyDivisionOfTaxationMember" xlink:label="us-gaap_NewJerseyDivisionOfTaxationMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeTaxAuthorityNameDomain" xlink:to="us-gaap_NewJerseyDivisionOfTaxationMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementLineItems" xlink:label="us-gaap_StatementLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CurrentStateAndLocalTaxExpenseBenefit" xlink:label="us-gaap_CurrentStateAndLocalTaxExpenseBenefit" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_CurrentStateAndLocalTaxExpenseBenefit" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_ProceedsFromSaleOfOperatingLossesAndTaxCredits" xlink:label="cldx_ProceedsFromSaleOfOperatingLossesAndTaxCredits" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_StatementLineItems" xlink:to="cldx_ProceedsFromSaleOfOperatingLossesAndTaxCredits" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_PeriodForWhichBaseOfOperationsMustBeMaintained" xlink:label="cldx_PeriodForWhichBaseOfOperationsMustBeMaintained" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_StatementLineItems" xlink:to="cldx_PeriodForWhichBaseOfOperationsMustBeMaintained" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_InterestAndOtherIncome" xlink:label="us-gaap_InterestAndOtherIncome" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_StatementLineItems" xlink:to="us-gaap_InterestAndOtherIncome" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilitiesLeaseRestructureDetails" xlink:type="extended" xlink:title="40603 - Disclosure - Other Long-Term Liabilities - Lease Restructure (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementTable" xlink:label="us-gaap_StatementTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_IncomeStatementLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain_636452534767053021" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain_636452534767053021" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_GeneralAndAdministrativeExpenseMember" xlink:label="us-gaap_GeneralAndAdministrativeExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_GeneralAndAdministrativeExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RestructuringCostAndReserveAxis" xlink:label="us-gaap_RestructuringCostAndReserveAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_StatementTable" xlink:to="us-gaap_RestructuringCostAndReserveAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_TypeOfRestructuringDomain" xlink:label="us-gaap_TypeOfRestructuringDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_RestructuringCostAndReserveAxis" xlink:to="us-gaap_TypeOfRestructuringDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_TypeOfRestructuringDomain" xlink:label="us-gaap_TypeOfRestructuringDomain_636452534767053021" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_RestructuringCostAndReserveAxis" xlink:to="us-gaap_TypeOfRestructuringDomain_636452534767053021" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_FacilityClosingMember" xlink:label="us-gaap_FacilityClosingMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_TypeOfRestructuringDomain" xlink:to="us-gaap_FacilityClosingMember" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_NeedhamMassachusettsExpansionSpaceMember" xlink:label="cldx_NeedhamMassachusettsExpansionSpaceMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_TypeOfRestructuringDomain" xlink:to="cldx_NeedhamMassachusettsExpansionSpaceMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RestructuringCostAndReserveLineItems" xlink:label="us-gaap_RestructuringCostAndReserveLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_RestructuringCostAndReserveLineItems" xlink:to="us-gaap_StatementTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AreaOfLand" xlink:label="us-gaap_AreaOfLand" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RestructuringCostAndReserveLineItems" xlink:to="us-gaap_AreaOfLand" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RestructuringReserveAbstract" xlink:label="us-gaap_RestructuringReserveAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_RestructuringCostAndReserveLineItems" xlink:to="us-gaap_RestructuringReserveAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RestructuringReserve" xlink:label="us-gaap_RestructuringReserve" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RestructuringReserveAbstract" xlink:to="us-gaap_RestructuringReserve" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RestructuringCharges" xlink:label="us-gaap_RestructuringCharges" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RestructuringReserveAbstract" xlink:to="us-gaap_RestructuringCharges" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_PaymentsForRestructuring" xlink:label="us-gaap_PaymentsForRestructuring" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_RestructuringReserveAbstract" xlink:to="us-gaap_PaymentsForRestructuring" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureStockholdersEquityDetails" xlink:type="extended" xlink:title="40701 - Disclosure - Stockholders' Equity (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_StockholdersEquityTable" xlink:label="cldx_StockholdersEquityTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SubsidiarySaleOfStockAxis" xlink:label="us-gaap_SubsidiarySaleOfStockAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="cldx_StockholdersEquityTable" xlink:to="us-gaap_SubsidiarySaleOfStockAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SaleOfStockNameOfTransactionDomain" xlink:label="us-gaap_SaleOfStockNameOfTransactionDomain_636452534767073023" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_SubsidiarySaleOfStockAxis" xlink:to="us-gaap_SaleOfStockNameOfTransactionDomain_636452534767073023" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_ControlledEquityOfferingSalesAgreementMember" xlink:label="cldx_ControlledEquityOfferingSalesAgreementMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SaleOfStockNameOfTransactionDomain" xlink:to="cldx_ControlledEquityOfferingSalesAgreementMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="cldx_StockholdersEquityTable" xlink:to="us-gaap_StatementEquityComponentsAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain_636452534767083024" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain_636452534767083024" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CommonStockMember" xlink:label="us-gaap_CommonStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_CommonStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SubsequentEventTypeAxis" xlink:label="us-gaap_SubsequentEventTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="3" xlink:from="cldx_StockholdersEquityTable" xlink:to="us-gaap_SubsequentEventTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SubsequentEventTypeDomain" xlink:label="us-gaap_SubsequentEventTypeDomain_636452534767083024" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_SubsequentEventTypeAxis" xlink:to="us-gaap_SubsequentEventTypeDomain_636452534767083024" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SubsequentEventMember" xlink:label="us-gaap_SubsequentEventMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_SubsequentEventTypeDomain" xlink:to="us-gaap_SubsequentEventMember" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_StockholdersEquityLineItems" xlink:label="cldx_StockholdersEquityLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="cldx_StockholdersEquityLineItems" xlink:to="cldx_StockholdersEquityTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_StockIssuedAuthorizedAmount" xlink:label="cldx_StockIssuedAuthorizedAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="cldx_StockholdersEquityLineItems" xlink:to="cldx_StockIssuedAuthorizedAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StockIssuedDuringPeriodSharesNewIssues" xlink:label="us-gaap_StockIssuedDuringPeriodSharesNewIssues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="cldx_StockholdersEquityLineItems" xlink:to="us-gaap_StockIssuedDuringPeriodSharesNewIssues" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ProceedsFromIssuanceOfCommonStock" xlink:label="us-gaap_ProceedsFromIssuanceOfCommonStock" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="cldx_StockholdersEquityLineItems" xlink:to="us-gaap_ProceedsFromIssuanceOfCommonStock" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_StockIssuedRemainingAuthorizedAmount" xlink:label="cldx_StockIssuedRemainingAuthorizedAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="cldx_StockholdersEquityLineItems" xlink:to="cldx_StockIssuedRemainingAuthorizedAmount" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationSummaryOfPlansDetails" xlink:type="extended" xlink:title="40801 - Disclosure - Stock-Based Compensation - Summary of Plans (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:label="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_636452534767103026" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain_636452534767103026" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" xlink:label="cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfShareBasedCompensationArrangementsByShareBasedPaymentAwardTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodGross" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsForfeituresInPeriod" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableNumber" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingRollForward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardNumberOfSharesAvailableForGrant" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardOptionsForfeituresInPeriodWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsVestedAndExpectedToVestOutstandingWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsOutstandingWeightedAverageExercisePriceRollforward" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsExercisableWeightedAverageExercisePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" xlink:label="cldx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="cldx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="cldx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsOutstandingWeightedAverageRemainingContractualTerm2" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="cldx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsVestedAndExpectedToVestExercisableWeightedAverageRemainingContractualTerm1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="cldx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardOptionsExercisableWeightedAverageRemainingContractualTerm1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsGrantsInPeriodWeightedAverageGrantDateFairValue" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationExpenseDetails" xlink:type="extended" xlink:title="40802 - Disclosure - Stock-Based Compensation - Expense (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeStatementLocationAxis" xlink:label="us-gaap_IncomeStatementLocationAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="us-gaap_IncomeStatementLocationAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_IncomeStatementLocationDomain" xlink:label="us-gaap_IncomeStatementLocationDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_IncomeStatementLocationAxis" xlink:to="us-gaap_IncomeStatementLocationDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ResearchAndDevelopmentExpenseMember" xlink:label="us-gaap_ResearchAndDevelopmentExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_ResearchAndDevelopmentExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_GeneralAndAdministrativeExpenseMember" xlink:label="us-gaap_GeneralAndAdministrativeExpenseMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_IncomeStatementLocationDomain" xlink:to="us-gaap_GeneralAndAdministrativeExpenseMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:label="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AllocatedShareBasedCompensationExpense" xlink:label="us-gaap_AllocatedShareBasedCompensationExpense" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsLineItems" xlink:to="us-gaap_AllocatedShareBasedCompensationExpense" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationValuationDetails" xlink:type="extended" xlink:title="40803 - Disclosure - Stock-Based Compensation - Valuation (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:label="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AwardTypeAxis" xlink:label="us-gaap_AwardTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" xlink:to="us-gaap_AwardTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:label="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AwardTypeAxis" xlink:to="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" xlink:label="cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementsByShareBasedPaymentAwardAwardTypeAndPlanNameDomain" xlink:to="cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ScheduleOfEmployeeServiceShareBasedCompensationAllocationOfRecognizedPeriodCostsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardLineItems" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMinimum" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedVolatilityRateMaximum" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" xlink:label="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_SharebasedCompensationArrangementBySharebasedPaymentAwardFairValueAssumptionsExpectedTerm1" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRate" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMinimum" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsRiskFreeInterestRateMaximum" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" xlink:label="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsAndMethodologyAbstract" xlink:to="us-gaap_ShareBasedCompensationArrangementByShareBasedPaymentAwardFairValueAssumptionsExpectedDividendRate" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureAccumulatedOtherComprehensiveIncomeDetails" xlink:type="extended" xlink:title="40901 - Disclosure - Accumulated Other Comprehensive Income (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossTable" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StatementEquityComponentsAxis" xlink:label="us-gaap_StatementEquityComponentsAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_AccumulatedOtherComprehensiveIncomeLossTable" xlink:to="us-gaap_StatementEquityComponentsAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_EquityComponentDomain" xlink:label="us-gaap_EquityComponentDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_StatementEquityComponentsAxis" xlink:to="us-gaap_EquityComponentDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccumulatedNetUnrealizedInvestmentGainLossMember" xlink:label="us-gaap_AccumulatedNetUnrealizedInvestmentGainLossMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AccumulatedNetUnrealizedInvestmentGainLossMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccumulatedTranslationAdjustmentMember" xlink:label="us-gaap_AccumulatedTranslationAdjustmentMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AccumulatedTranslationAdjustmentMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeMember" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_EquityComponentDomain" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems" xlink:label="us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems" xlink:to="us-gaap_AccumulatedOtherComprehensiveIncomeLossTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_AccumulatedOtherComprehensiveIncomeLossRollForward" xlink:label="cldx_AccumulatedOtherComprehensiveIncomeLossRollForward" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AccumulatedOtherComprehensiveIncomeLossLineItems" xlink:to="cldx_AccumulatedOtherComprehensiveIncomeLossRollForward" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax" xlink:label="us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="cldx_AccumulatedOtherComprehensiveIncomeLossRollForward" xlink:to="us-gaap_ReclassificationFromAccumulatedOtherComprehensiveIncomeCurrentPeriodNetOfTax" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_StockholdersEquity" xlink:label="us-gaap_StockholdersEquity" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="cldx_AccumulatedOtherComprehensiveIncomeLossRollForward" xlink:to="us-gaap_StockholdersEquity" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_OtherComprehensiveIncomeLossNetOfTax" xlink:label="us-gaap_OtherComprehensiveIncomeLossNetOfTax" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="cldx_AccumulatedOtherComprehensiveIncomeLossRollForward" xlink:to="us-gaap_OtherComprehensiveIncomeLossNetOfTax" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureRevenueDetails" xlink:type="extended" xlink:title="41001 - Disclosure - Revenue (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:label="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CounterpartyNameAxis" xlink:label="us-gaap_CounterpartyNameAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" xlink:to="us-gaap_CounterpartyNameAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:label="us-gaap_RepurchaseAgreementCounterpartyNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_CounterpartyNameAxis" xlink:to="us-gaap_RepurchaseAgreementCounterpartyNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:label="us-gaap_RepurchaseAgreementCounterpartyNameDomain_636452534767223038" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_CounterpartyNameAxis" xlink:to="us-gaap_RepurchaseAgreementCounterpartyNameDomain_636452534767223038" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_RockefellerMember" xlink:label="cldx_RockefellerMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:to="cldx_RockefellerMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_BristolMeyersSquibbCompanyMember" xlink:label="cldx_BristolMeyersSquibbCompanyMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:to="cldx_BristolMeyersSquibbCompanyMember" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_InternationalAidsVaccineInitiativeMember" xlink:label="cldx_InternationalAidsVaccineInitiativeMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:to="cldx_InternationalAidsVaccineInitiativeMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_FrontierBiotechnologiesIncMember" xlink:label="cldx_FrontierBiotechnologiesIncMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_RepurchaseAgreementCounterpartyNameDomain" xlink:to="cldx_FrontierBiotechnologiesIncMember" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:label="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_ScheduleOfCollaborativeArrangementsAndNoncollaborativeArrangementTransactionsTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_CollaborativeArrangementAgreementTerm" xlink:label="cldx_CollaborativeArrangementAgreementTerm" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="cldx_CollaborativeArrangementAgreementTerm" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_DeferredRevenue" xlink:label="us-gaap_DeferredRevenue" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_DeferredRevenue" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_ReimbursementOfExternalCostsIncurredPercentage" xlink:label="cldx_ReimbursementOfExternalCostsIncurredPercentage" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="cldx_ReimbursementOfExternalCostsIncurredPercentage" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_Revenues" xlink:label="us-gaap_Revenues" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_CollaborativeArrangementsAndNoncollaborativeArrangementTransactionsLineItems" xlink:to="us-gaap_Revenues" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureKolltanAcquisitionPurchasePriceDetails" xlink:type="extended" xlink:title="41101 - Disclosure - Kolltan Acquisition- Purchase Price (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_BusinessAcquisitionAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_KolltanPharmaceuticalsMember" xlink:label="cldx_KolltanPharmaceuticalsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="cldx_KolltanPharmaceuticalsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContingentConsiderationByTypeAxis" xlink:label="us-gaap_ContingentConsiderationByTypeAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="2" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_ContingentConsiderationByTypeAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ContingentConsiderationTypeDomain" xlink:label="us-gaap_ContingentConsiderationTypeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_ContingentConsiderationByTypeAxis" xlink:to="us-gaap_ContingentConsiderationTypeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_ContingentMilestoneMember" xlink:label="cldx_ContingentMilestoneMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_ContingentConsiderationTypeDomain" xlink:to="cldx_ContingentMilestoneMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionLineItems" xlink:label="us-gaap_BusinessAcquisitionLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionEquityInterestsIssuedOrIssuableNumberOfSharesIssued" xlink:label="us-gaap_BusinessAcquisitionEquityInterestsIssuedOrIssuableNumberOfSharesIssued" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessAcquisitionEquityInterestsIssuedOrIssuableNumberOfSharesIssued" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_BusinessAcquisitionStockIssuableInLieuOfSeverance" xlink:label="cldx_BusinessAcquisitionStockIssuableInLieuOfSeverance" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="cldx_BusinessAcquisitionStockIssuableInLieuOfSeverance" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_BusinessAcquisitionStockIssuedInLieuOfSeverance" xlink:label="cldx_BusinessAcquisitionStockIssuedInLieuOfSeverance" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="cldx_BusinessAcquisitionStockIssuedInLieuOfSeverance" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_BusinessAcquisitionRemainingStockObligation" xlink:label="cldx_BusinessAcquisitionRemainingStockObligation" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="cldx_BusinessAcquisitionRemainingStockObligation" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" xlink:label="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationContingentConsiderationArrangementsRangeOfOutcomesValueHigh" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_SharePrice" xlink:label="us-gaap_SharePrice" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_SharePrice" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationConsiderationTransferredAbstract" xlink:label="us-gaap_BusinessCombinationConsiderationTransferredAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationConsiderationTransferredAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuable" xlink:label="us-gaap_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuable" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BusinessCombinationConsiderationTransferredAbstract" xlink:to="us-gaap_BusinessCombinationConsiderationTransferredEquityInterestsIssuedAndIssuable" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationContingentConsiderationLiability" xlink:label="us-gaap_BusinessCombinationContingentConsiderationLiability" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_BusinessCombinationConsiderationTransferredAbstract" xlink:to="us-gaap_BusinessCombinationContingentConsiderationLiability" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationAcquisitionRelatedCosts" xlink:label="us-gaap_BusinessCombinationAcquisitionRelatedCosts" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_BusinessCombinationConsiderationTransferredAbstract" xlink:to="us-gaap_BusinessCombinationAcquisitionRelatedCosts" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationConsiderationTransferred1" xlink:label="us-gaap_BusinessCombinationConsiderationTransferred1" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_BusinessCombinationConsiderationTransferredAbstract" xlink:to="us-gaap_BusinessCombinationConsiderationTransferred1" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureKolltanAcquisitionAllocationsOfAssetsAndLiabilitiesDetails" xlink:type="extended" xlink:title="41102 - Disclosure - Kolltan Acquisition - Allocations of Assets and Liabilities (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:label="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAxis" xlink:label="us-gaap_BusinessAcquisitionAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" xlink:to="us-gaap_BusinessAcquisitionAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionAcquireeDomain" xlink:label="us-gaap_BusinessAcquisitionAcquireeDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_BusinessAcquisitionAxis" xlink:to="us-gaap_BusinessAcquisitionAcquireeDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_KolltanPharmaceuticalsMember" xlink:label="cldx_KolltanPharmaceuticalsMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BusinessAcquisitionAcquireeDomain" xlink:to="cldx_KolltanPharmaceuticalsMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionLineItems" xlink:label="us-gaap_BusinessAcquisitionLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_ScheduleOfBusinessAcquisitionsByAcquisitionTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionPurchasePriceAllocationGoodwillExpectedTaxDeductibleAmount" xlink:label="us-gaap_BusinessAcquisitionPurchasePriceAllocationGoodwillExpectedTaxDeductibleAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessAcquisitionPurchasePriceAllocationGoodwillExpectedTaxDeductibleAmount" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_BusinessAcquisitionLineItems" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedCashAndEquivalents" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherCurrentAndLongTermAssets" xlink:label="cldx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherCurrentAndLongTermAssets" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="cldx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherCurrentAndLongTermAssets" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="3" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedPropertyPlantAndEquipment" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="4" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedIndefiniteLivedIntangibleAssets" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_Goodwill" xlink:label="us-gaap_Goodwill" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="5" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="us-gaap_Goodwill" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="6" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedDeferredTaxLiabilities" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherLiabilities" xlink:label="cldx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherLiabilities" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="7" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="cldx_BusinessCombinationRecognizedIdentifiableAssetsAcquiredAndLiabilitiesAssumedOtherLiabilities" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" xlink:label="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="8" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNet" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionProFormaInformationAbstract" xlink:label="us-gaap_BusinessAcquisitionProFormaInformationAbstract" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="9" xlink:from="us-gaap_BusinessCombinationRecognizedIdentifiableAssetsAcquiredGoodwillAndLiabilitiesAssumedNetAbstract" xlink:to="us-gaap_BusinessAcquisitionProFormaInformationAbstract" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss" xlink:label="us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_BusinessAcquisitionProFormaInformationAbstract" xlink:to="us-gaap_BusinessAcquisitionsProFormaNetIncomeLoss" priority="1" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_BusinessAcquisitionProFormaEarningsPerShareBasicAndDiluted" xlink:label="cldx_BusinessAcquisitionProFormaEarningsPerShareBasicAndDiluted" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_BusinessAcquisitionProFormaInformationAbstract" xlink:to="cldx_BusinessAcquisitionProFormaEarningsPerShareBasicAndDiluted" priority="1" use="optional" />
  </definitionLink>
  <definitionLink xlink:role="http://www.celldextherapeutics.com/role/DisclosureNetLossPerShareDetails" xlink:type="extended" xlink:title="41301 - Disclosure - Net Loss Per Share (Details)" xmlns="http://www.xbrl.org/2003/linkbase">
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:label="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/hypercube-dimension" order="1" xlink:from="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-domain" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AntidilutiveSecuritiesNameDomain" xlink:label="us-gaap_AntidilutiveSecuritiesNameDomain_636452534767303046" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/dimension-default" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareByAntidilutiveSecuritiesAxis" xlink:to="us-gaap_AntidilutiveSecuritiesNameDomain_636452534767303046" use="optional" />
    <loc xlink:type="locator" xlink:href="cldx-20170930.xsd#cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" xlink:label="cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="cldx_EmployeeConsultantAndNonEmployeeDirectorStockOptionMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_RestrictedStockMember" xlink:label="us-gaap_RestrictedStockMember" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AntidilutiveSecuritiesNameDomain" xlink:to="us-gaap_RestrictedStockMember" use="optional" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/all" order="1" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_ScheduleOfAntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareTable" use="optional" xbrldt:contextElement="segment" xbrldt:closed="true" />
    <loc xlink:type="locator" xlink:href="http://xbrl.fasb.org/us-gaap/2016/elts/us-gaap-2016-01-31.xsd#us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" xlink:label="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" />
    <definitionArc xlink:type="arc" xlink:arcrole="http://xbrl.org/int/dim/arcrole/domain-member" order="2" xlink:from="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareLineItems" xlink:to="us-gaap_AntidilutiveSecuritiesExcludedFromComputationOfEarningsPerShareAmount" priority="1" use="optional" />
  </definitionLink>
</link:linkbase>
