<?xml version="1.0" encoding="utf-8"?>
<!--XBRL document created with Toppan Merrill Bridge  10.10.0.1 -->
<!--Based on XBRL 2.1-->
<!--Created on: 5/1/2025 7:38:21 PM-->
<!--Modified on: 5/1/2025 7:38:21 PM-->
<xsd:schema targetNamespace="http://www.celldextherapeutics.com/20250331" attributeFormDefault="unqualified" elementFormDefault="qualified" xmlns:xsd="http://www.w3.org/2001/XMLSchema" xmlns:ref="http://www.xbrl.org/2006/ref" xmlns:xbrldt="http://xbrl.org/2005/xbrldt" xmlns:xl="http://www.xbrl.org/2003/XLink" xmlns:link="http://www.xbrl.org/2003/linkbase" xmlns:net="http://www.xbrl.org/2009/role/net" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:attributeFormDefault="unqualified" xmlns:xbrli="http://www.xbrl.org/2003/instance" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:us-gaap="http://fasb.org/us-gaap/2024" xmlns:us-types="http://fasb.org/us-types/2024" xmlns:us-roles="http://fasb.org/us-roles/2024" xmlns:negated="http://www.xbrl.org/2009/role/negated" xmlns:srt-types="http://fasb.org/srt-types/2024" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2022-03-31" xmlns:cldx="http://www.celldextherapeutics.com/20250331" xmlns:enum2="http://xbrl.org/2020/extensible-enumerations-2.0" xmlns:currency="http://xbrl.sec.gov/currency/2024" xmlns:sic="http://xbrl.sec.gov/sic/2024" xmlns:srt-roles="http://fasb.org/srt-roles/2024" xmlns:stpr="http://xbrl.sec.gov/stpr/2024" xmlns:utr="http://www.xbrl.org/2009/utr" xmlns:exch="http://xbrl.sec.gov/exch/2024" xmlns:naics="http://xbrl.sec.gov/naics/2024" xmlns:country="http://xbrl.sec.gov/country/2024" xmlns:srt="http://fasb.org/srt/2024" xmlns:deprecated="http://www.xbrl.org/2009/role/deprecated" xmlns:dei="http://xbrl.sec.gov/dei/2024" xmlns:dtr="http://www.xbrl.org/2009/dtr" xmlns:xbrldi="http://xbrl.org/2006/xbrldi" xmlns:us-gaap-ebp="http://fasb.org/us-gaap-ebp/2024" xmlns:cyd-af-sub="http://xbrl.sec.gov/cyd-af-sub/2024" xmlns:ecd="http://xbrl.sec.gov/ecd/2024" xmlns:ecd-sub="http://xbrl.sec.gov/ecd-sub/2024">
  <xsd:annotation>
    <xsd:appinfo>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStandardAndCustomAxisDomainDefaults" id="DisclosureStandardAndCustomAxisDomainDefaults">
        <link:definition>99900 - Disclosure - Standard And Custom Axis Domain Defaults</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/StatementCondensedConsolidatedBalanceSheets" id="StatementCondensedConsolidatedBalanceSheets">
        <link:definition>995200100 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss" id="StatementCondensedConsolidatedStatementsOfOperationsAndComprehensiveLoss">
        <link:definition>995200200 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/StatementCondensedConsolidatedStatementsOfCashFlow" id="StatementCondensedConsolidatedStatementsOfCashFlow">
        <link:definition>995200300 - Statement - CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOW</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureSegmentInformationResearchAndDevelopmentExpensesDisaggregatedByNatureDetails" id="DisclosureSegmentInformationResearchAndDevelopmentExpensesDisaggregatedByNatureDetails">
        <link:definition>99940302 - Disclosure - Segment Information - Research and development expenses disaggregated by nature (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsDetails" id="DisclosureFairValueMeasurementsDetails">
        <link:definition>99940401 - Disclosure - Fair Value Measurements (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureMarketableSecuritiesDetails" id="DisclosureMarketableSecuritiesDetails">
        <link:definition>99940501 - Disclosure - Marketable Securities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilitiesDetails" id="DisclosureOtherLongTermLiabilitiesDetails">
        <link:definition>99940801 - Disclosure - Other Long-Term Liabilities (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DocumentDocumentAndEntityInformation" id="DocumentDocumentAndEntityInformation">
        <link:definition>995200090 - Document - Document and Entity Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/StatementCondensedConsolidatedBalanceSheetsParenthetical" id="StatementCondensedConsolidatedBalanceSheetsParenthetical">
        <link:definition>995200105 - Statement - CONDENSED CONSOLIDATED BALANCE SHEETS (Parenthetical)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureSegmentInformationResearchAndDevelopmentCostsAndAllocationOfIndirectResearchAndDevelopmentCostsToEachProgramDetails" id="DisclosureSegmentInformationResearchAndDevelopmentCostsAndAllocationOfIndirectResearchAndDevelopmentCostsToEachProgramDetails">
        <link:definition>99940301 - Disclosure - Segment Information - Research and development costs and an allocation of indirect research and development costs to each program (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsAdditionalInformationDetails" id="DisclosureFairValueMeasurementsAdditionalInformationDetails">
        <link:definition>99940402 - Disclosure - Fair Value Measurements - Additional information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureIntangibleAssetsDetails" id="DisclosureIntangibleAssetsDetails">
        <link:definition>99940601 - Disclosure - Intangible Assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilitiesAdditionalInformationDetails" id="DisclosureOtherLongTermLiabilitiesAdditionalInformationDetails">
        <link:definition>99940802 - Disclosure - Other Long-Term Liabilities - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockholdersEquityAdditionalInformationDetails" id="DisclosureStockholdersEquityAdditionalInformationDetails">
        <link:definition>99940901 - Disclosure - Stockholders' Equity - Additional information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockholdersEquityDetails" id="DisclosureStockholdersEquityDetails">
        <link:definition>99940902 - Disclosure - Stockholders' Equity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationStockOptionActivityDetails" id="DisclosureStockBasedCompensationStockOptionActivityDetails">
        <link:definition>99941001 - Disclosure - Stock-Based Compensation - Stock Option Activity (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationEmployeeStockOptionDetails" id="DisclosureStockBasedCompensationEmployeeStockOptionDetails">
        <link:definition>99941002 - Disclosure - Stock-Based Compensation - Employee Stock Option (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationExpensesDetails" id="DisclosureStockBasedCompensationExpensesDetails">
        <link:definition>99941003 - Disclosure - Stock-Based Compensation - Expenses (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationValuationDetails" id="DisclosureStockBasedCompensationValuationDetails">
        <link:definition>99941004 - Disclosure - Stock-Based Compensation - Valuation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureAccumulatedOtherComprehensiveIncomeDetails" id="DisclosureAccumulatedOtherComprehensiveIncomeDetails">
        <link:definition>99941101 - Disclosure - Accumulated Other Comprehensive Income (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureRevenueDetails" id="DisclosureRevenueDetails">
        <link:definition>99941201 - Disclosure - Revenue (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureIncomeTaxesDetails" id="DisclosureIncomeTaxesDetails">
        <link:definition>99941301 - Disclosure - Income Taxes (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureNetLossPerShareDetails" id="DisclosureNetLossPerShareDetails">
        <link:definition>99941401 - Disclosure - Net Loss Per Share (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureKolltanAcquisitionDetails" id="DisclosureKolltanAcquisitionDetails">
        <link:definition>99941501 - Disclosure - Kolltan Acquisition (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureBasisOfPresentation" id="DisclosureBasisOfPresentation">
        <link:definition>995210101 - Disclosure - Basis of Presentation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureSignificantAccountingPolicies" id="DisclosureSignificantAccountingPolicies">
        <link:definition>995210201 - Disclosure - Significant Accounting Policies</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureSegmentInformation" id="DisclosureSegmentInformation">
        <link:definition>995210301 - Disclosure - Segment Information</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurements" id="DisclosureFairValueMeasurements">
        <link:definition>995210401 - Disclosure - Fair Value Measurements</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureMarketableSecurities" id="DisclosureMarketableSecurities">
        <link:definition>995210501 - Disclosure - Marketable Securities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureIntangibleAssets" id="DisclosureIntangibleAssets">
        <link:definition>995210601 - Disclosure - Intangible Assets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherAssets" id="DisclosureOtherAssets">
        <link:definition>995210701 - Disclosure - Other Assets</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilities" id="DisclosureOtherLongTermLiabilities">
        <link:definition>995210801 - Disclosure - Other Long-Term Liabilities</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockholdersEquity" id="DisclosureStockholdersEquity">
        <link:definition>995210901 - Disclosure - Stockholders' Equity</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensation" id="DisclosureStockBasedCompensation">
        <link:definition>995211001 - Disclosure - Stock-Based Compensation</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureAccumulatedOtherComprehensiveIncome" id="DisclosureAccumulatedOtherComprehensiveIncome">
        <link:definition>995211101 - Disclosure - Accumulated Other Comprehensive Income</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureRevenue" id="DisclosureRevenue">
        <link:definition>995211201 - Disclosure - Revenue</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureIncomeTaxes" id="DisclosureIncomeTaxes">
        <link:definition>995211301 - Disclosure - Income Taxes</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureNetLossPerShare" id="DisclosureNetLossPerShare">
        <link:definition>995211401 - Disclosure - Net Loss Per Share</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureKolltanAcquisition" id="DisclosureKolltanAcquisition">
        <link:definition>995211501 - Disclosure - Kolltan Acquisition</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureSignificantAccountingPoliciesPolicies" id="DisclosureSignificantAccountingPoliciesPolicies">
        <link:definition>99920202 - Disclosure - Significant Accounting Policies (Policies)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureSegmentInformationTables" id="DisclosureSegmentInformationTables">
        <link:definition>99930303 - Disclosure - Segment Information (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureFairValueMeasurementsTables" id="DisclosureFairValueMeasurementsTables">
        <link:definition>99930403 - Disclosure - Fair Value Measurements (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureMarketableSecuritiesTables" id="DisclosureMarketableSecuritiesTables">
        <link:definition>99930503 - Disclosure - Marketable Securities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherLongTermLiabilitiesTables" id="DisclosureOtherLongTermLiabilitiesTables">
        <link:definition>99930803 - Disclosure - Other Long-Term Liabilities (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockholdersEquityTables" id="DisclosureStockholdersEquityTables">
        <link:definition>99930903 - Disclosure - Stockholders' Equity (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureStockBasedCompensationTables" id="DisclosureStockBasedCompensationTables">
        <link:definition>99931003 - Disclosure - Stock-Based Compensation (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureAccumulatedOtherComprehensiveIncomeTables" id="DisclosureAccumulatedOtherComprehensiveIncomeTables">
        <link:definition>99931103 - Disclosure - Accumulated Other Comprehensive Income (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureNetLossPerShareTables" id="DisclosureNetLossPerShareTables">
        <link:definition>99931403 - Disclosure - Net Loss Per Share (Tables)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureBasisOfPresentationDetails" id="DisclosureBasisOfPresentationDetails">
        <link:definition>99940101 - Disclosure - Basis of Presentation (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureMarketableSecuritiesAdditionalInformationDetails" id="DisclosureMarketableSecuritiesAdditionalInformationDetails">
        <link:definition>99940502 - Disclosure - Marketable Securities - Additional Information (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:roleType roleURI="http://www.celldextherapeutics.com/role/DisclosureOtherAssetsDetails" id="DisclosureOtherAssetsDetails">
        <link:definition>99940701 - Disclosure - Other Assets (Details)</link:definition>
        <link:usedOn>link:presentationLink</link:usedOn>
        <link:usedOn>link:calculationLink</link:usedOn>
        <link:usedOn>link:definitionLink</link:usedOn>
      </link:roleType>
      <link:linkbaseRef xlink:type="simple" xlink:href="cldx-20250331_pre.xml" xlink:role="http://www.xbrl.org/2003/role/presentationLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="cldx-20250331_cal.xml" xlink:role="http://www.xbrl.org/2003/role/calculationLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="cldx-20250331_def.xml" xlink:role="http://www.xbrl.org/2003/role/definitionLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
      <link:linkbaseRef xlink:type="simple" xlink:href="cldx-20250331_lab.xml" xlink:role="http://www.xbrl.org/2003/role/labelLinkbaseRef" xlink:arcrole="http://www.w3.org/1999/xlink/properties/linkbase" />
    </xsd:appinfo>
  </xsd:annotation>
  <xsd:import namespace="https://xbrl.org/2023/calculation-1.1" schemaLocation="https://www.xbrl.org/2023/calculation-1.1.xsd" />
  <xsd:import namespace="http://xbrl.sec.gov/ecd/2024" schemaLocation="https://xbrl.sec.gov/ecd/2024/ecd-2024.xsd" />
  <xsd:import namespace="http://xbrl.sec.gov/dei/2024" schemaLocation="https://xbrl.sec.gov/dei/2024/dei-2024.xsd" />
  <xsd:import namespace="http://www.xbrl.org/dtr/type/2022-03-31" schemaLocation="https://www.xbrl.org/dtr/type/2022-03-31/types.xsd" />
  <xsd:import namespace="http://www.xbrl.org/2009/role/negated" schemaLocation="http://www.xbrl.org/lrr/role/negated-2009-12-16.xsd" />
  <xsd:import namespace="http://fasb.org/us-roles/2024" schemaLocation="https://xbrl.fasb.org/us-gaap/2024/elts/us-roles-2024.xsd" />
  <xsd:import namespace="http://www.xbrl.org/2003/instance" schemaLocation="http://www.xbrl.org/2003/xbrl-instance-2003-12-31.xsd" />
  <xsd:import namespace="http://xbrl.org/2005/xbrldt" schemaLocation="http://www.xbrl.org/2005/xbrldt-2005.xsd" />
  <xsd:import namespace="http://fasb.org/us-gaap/2024" schemaLocation="https://xbrl.fasb.org/us-gaap/2024/elts/us-gaap-2024.xsd" />
  <xsd:import namespace="http://fasb.org/srt/2024" schemaLocation="https://xbrl.fasb.org/srt/2024/elts/srt-2024.xsd" />
  <xsd:import namespace="http://xbrl.sec.gov/ecd-sub/2024" schemaLocation="https://xbrl.sec.gov/ecd/2024/ecd-sub-2024.xsd" />
  <xsd:element id="cldx_DeferredIncomeFromSaleOfTaxBenefits" name="DeferredIncomeFromSaleOfTaxBenefits" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element name="PeriodForWhichBaseOfOperationsMustBeMaintained" id="cldx_PeriodForWhichBaseOfOperationsMustBeMaintained" type="xbrli:durationItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" />
  <xsd:element name="ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" id="cldx_ShareBasedCompensationArrangementByShareBasedPaymentAwardOptionsWeightedAverageRemainingContractualTermAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" nillable="true" xbrli:periodType="duration" />
  <xsd:element id="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsAmortizedCost" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsAmortizedCost" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedGain" name="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedGain" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element id="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsGrossUnrealizedGain" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsGrossUnrealizedGain" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <xsd:element name="AvailableForSaleSecuritiesGrossUnrealizedLossesAbstract" id="cldx_AvailableForSaleSecuritiesGrossUnrealizedLossesAbstract" type="xbrli:stringItemType" substitutionGroup="xbrli:item" abstract="true" nillable="true" xbrli:periodType="duration" />
  <xsd:element id="cldx_AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedLosses" name="AvailableForSaleSecuritiesDebtMaturitiesWithinOneYearGrossUnrealizedLosses" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsGrossUnrealizedLosses" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsGrossUnrealizedLosses" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="cldx_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsFairValue" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsFairValue" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="cldx_ProceedsFromSaleOfOperatingLossesAndTaxCredits" name="ProceedsFromSaleOfOperatingLossesAndTaxCredits" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" xbrli:balance="debit" />
  <xsd:element id="cldx_UnderwrittenPublicOfferingMember" name="UnderwrittenPublicOfferingMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="cldx_KolltanPharmaceuticalsMember" name="KolltanPharmaceuticalsMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element id="cldx_ContingentMilestoneMember" name="ContingentMilestoneMember" nillable="true" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" abstract="true" xbrli:periodType="duration" />
  <xsd:element name="BusinessCombinationContingentConsiderationSettlementAgreementAmountPaid" id="cldx_BusinessCombinationContingentConsiderationSettlementAgreementAmountPaid" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="BusinessCombinationContingentConsiderationSettlementAgreementAmountPayable" id="cldx_BusinessCombinationContingentConsiderationSettlementAgreementAmountPayable" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="NumberOfInvestmentGradeMarketableSecuritiesConsideredToBeOtherThanTemporarilyImpaired" id="cldx_NumberOfInvestmentGradeMarketableSecuritiesConsideredToBeOtherThanTemporarilyImpaired" type="xbrli:integerItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" />
  <xsd:element name="NewJerseyEconomicDevelopmentAuthorityMember" id="cldx_NewJerseyEconomicDevelopmentAuthorityMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="RockefellerUniversityMember" id="cldx_RockefellerUniversityMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="CashOutflowForMilestonePaymentsMadeUponSuccessfulCompletionOfClinicalTrial" id="cldx_CashOutflowForMilestonePaymentsMadeUponSuccessfulCompletionOfClinicalTrial" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="OtherNonCurrentLiabilitiesTable" id="cldx_OtherNonCurrentLiabilitiesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="OtherNonCurrentLiabilitiesLineItems" id="cldx_OtherNonCurrentLiabilitiesLineItems" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="CommonStockAmountReservedForFutureIssuance" id="cldx_CommonStockAmountReservedForFutureIssuance" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="instant" abstract="false" xbrli:balance="credit" />
  <xsd:element name="EquityOfferingSalesAgreementMember" id="cldx_EquityOfferingSalesAgreementMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="SingleReportableSegmentMember" id="cldx_SingleReportableSegmentMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="BarzolvolimabAntiKitProgramMember" id="cldx_BarzolvolimabAntiKitProgramMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="Cdx622ProgramMember" id="cldx_Cdx622ProgramMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="OtherProgramsMember" id="cldx_OtherProgramsMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="FacilityExpense" id="cldx_FacilityExpense" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
  <xsd:element name="ProductDevelopmentExpense" id="cldx_ProductDevelopmentExpense" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="debit" />
</xsd:schema>
