<?xml version="1.0" encoding="us-ascii"?>
<!--XBRL document created with Toppan Merrill Bridge  10.2.5.9 -->
<!--Based on XBRL 2.1-->
<!--Created on: 5/3/2023 10:39:02 PM-->
<!--Modified on: 5/3/2023 10:39:02 PM-->
<xsd:schema targetNamespace="http://www.celldextherapeutics.com/20230331" 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/2022" xmlns:us-types="http://fasb.org/us-types/2022" xmlns:us-roles="http://fasb.org/us-roles/2022" xmlns:negated="http://www.xbrl.org/2009/role/negated" xmlns:srt-types="http://fasb.org/srt-types/2022" xmlns:dtr-types="http://www.xbrl.org/dtr/type/2020-01-21" xmlns:cldx="http://www.celldextherapeutics.com/20230331" xmlns:enum2="http://xbrl.org/2020/extensible-enumerations-2.0" xmlns:currency="http://xbrl.sec.gov/currency/2022" xmlns:sic="http://xbrl.sec.gov/sic/2022" xmlns:srt-roles="http://fasb.org/srt-roles/2022" xmlns:stpr="http://xbrl.sec.gov/stpr/2022" xmlns:utr="http://www.xbrl.org/2009/utr" xmlns:exch="http://xbrl.sec.gov/exch/2022" xmlns:naics="http://xbrl.sec.gov/naics/2022" xmlns:country="http://xbrl.sec.gov/country/2022" xmlns:srt="http://fasb.org/srt/2022" xmlns:deprecated="http://www.xbrl.org/2009/role/deprecated" xmlns:dei="http://xbrl.sec.gov/dei/2022" xmlns:dtr="http://www.xbrl.org/2009/dtr" xmlns:cef="http://xbrl.sec.gov/cef/2022" xmlns:xbrldi="http://xbrl.org/2006/xbrldi">
  <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>00100 - 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>00200 - 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>00300 - 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/DisclosureFairValueMeasurementsDetails" id="DisclosureFairValueMeasurementsDetails">
        <link:definition>40301 - 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>40401 - 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>40601 - 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/DisclosureOtherLongTermLiabilitiesDetailsCalc2" id="DisclosureOtherLongTermLiabilitiesDetailsCalc2">
        <link:definition>40701 - Disclosure - Other Long-Term Liabilities (Details) (Calc 2)</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>00090 - 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>00105 - 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/DisclosureFairValueMeasurementsAdditionalInformationDetails" id="DisclosureFairValueMeasurementsAdditionalInformationDetails">
        <link:definition>40302 - 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>40501 - 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/DisclosureOtherLongTermLiabilitiesNewJerseyTaxBenefitsDetails" id="DisclosureOtherLongTermLiabilitiesNewJerseyTaxBenefitsDetails">
        <link:definition>40602 - Disclosure - Other Long-Term Liabilities- New Jersey tax benefits (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>40701 - 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>40801 - 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/DisclosureStockBasedCompensationEmployeeStockOptionAndIncentivePlanDetails" id="DisclosureStockBasedCompensationEmployeeStockOptionAndIncentivePlanDetails">
        <link:definition>40802 - Disclosure - Stock-Based Compensation - Employee Stock Option and Incentive Plan (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>40803 - 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>40804 - 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>40901 - 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>41001 - 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/DisclosureIncomeTaxesCarryforwardsDetails" id="DisclosureIncomeTaxesCarryforwardsDetails">
        <link:definition>41101 - Disclosure - Income Taxes - Carryforwards (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>41201 - 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>41301 - 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>10101 - 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>10201 - 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/DisclosureFairValueMeasurements" id="DisclosureFairValueMeasurements">
        <link:definition>10301 - 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>10401 - 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>10501 - 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/DisclosureOtherLongTermLiabilities" id="DisclosureOtherLongTermLiabilities">
        <link:definition>10601 - 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>10701 - 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>10801 - 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>10901 - 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>11001 - 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>11101 - 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>11201 - 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>11301 - 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>20202 - 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/DisclosureFairValueMeasurementsTables" id="DisclosureFairValueMeasurementsTables">
        <link:definition>30303 - 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>30403 - 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>30603 - 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>30703 - 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>30803 - 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>30903 - 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>31203 - 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>40101 - 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>40402 - 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:linkbaseRef xlink:type="simple" xlink:href="cldx-20230331_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-20230331_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-20230331_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-20230331_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="http://xbrl.sec.gov/dei/2022" schemaLocation="https://xbrl.sec.gov/dei/2022/dei-2022.xsd" />
  <xsd:import namespace="http://www.xbrl.org/dtr/type/2020-01-21" schemaLocation="https://www.xbrl.org/dtr/type/2020-01-21/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/2022" schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-roles-2022.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/2022" schemaLocation="https://xbrl.fasb.org/us-gaap/2022/elts/us-gaap-2022.xsd" />
  <xsd:import namespace="http://fasb.org/srt/2022" schemaLocation="https://xbrl.fasb.org/srt/2022/elts/srt-2022.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_AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsFairValue" name="AvailableForSaleSecuritiesDebtMaturitiesAfterOneThroughThreeYearsFairValue" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="debit" />
  <xsd:element id="cldx_NewlyAdoptedAccountingPronouncementsPolicyPolicyTextBlock" name="NewlyAdoptedAccountingPronouncementsPolicyPolicyTextBlock" nillable="true" type="dtr-types:textBlockItemType" substitutionGroup="xbrli:item" xbrli:periodType="duration" />
  <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_StockIssuedRemainingAuthorizedAmount" name="StockIssuedRemainingAuthorizedAmount" nillable="true" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" xbrli:periodType="instant" xbrli:balance="credit" />
  <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="EuropeanMedicinesAgencyMember" id="cldx_EuropeanMedicinesAgencyMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <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="ClinicalTrailMember" id="cldx_ClinicalTrailMember" type="dtr-types:domainItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="BusinessCombinationContingentConsiderationContractualCreditInMergerAgreement" id="cldx_BusinessCombinationContingentConsiderationContractualCreditInMergerAgreement" type="xbrli:monetaryItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="false" xbrli:balance="credit" />
  <xsd:element name="OtherLongTermLiabilitiesTable" id="cldx_OtherLongTermLiabilitiesTable" type="xbrli:stringItemType" substitutionGroup="xbrldt:hypercubeItem" nillable="true" xbrli:periodType="duration" abstract="true" />
  <xsd:element name="OtherLongTermLiabilitiesLineItem" id="cldx_OtherLongTermLiabilitiesLineItem" type="xbrli:stringItemType" substitutionGroup="xbrli:item" nillable="true" xbrli:periodType="duration" abstract="true" />
  <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:schema>
