<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0508</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2023-07-31</periodOfReport>

    <issuer>
        <issuerCik>0001829802</issuerCik>
        <issuerName>Sensei Biotherapeutics, Inc.</issuerName>
        <issuerTradingSymbol>SNSE</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001797409</rptOwnerCik>
            <rptOwnerName>Cambrian BioPharma Inc</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>228 PARK AVENUE S. #66643</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>NEW YORK</rptOwnerCity>
            <rptOwnerState>NY</rptOwnerState>
            <rptOwnerZipCode>10003</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isTenPercentOwner>true</isTenPercentOwner>
            <isOther>true</isOther>
            <otherText>See Remarks</otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2023-07-31</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>D</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>1587302</value>
                    <footnoteId id="F1"/>
                </transactionShares>
                <transactionPricePerShare>
                    <value>1.26</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>3653120</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>D</value>
                    <footnoteId id="F2"/>
                </directOrIndirectOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <footnotes>
        <footnote id="F1">Shares purchased by the Issuer pursuant to a Purchase Agreement, dated July 31, 2023, by and among the Issuer, the Reporting Person and James Peyer.  This transaction, which was approved by the Board of Directors of the Issuer, is exempt pursuant to Rule 16b-3(e) of the Securities Exchange Act of 1934, as amended.</footnote>
        <footnote id="F2">These shares are held by Cambrian Biopharma, Inc., a Delaware corporation (&quot;Cambrian&quot;). The Chief Executive Officer of Cambrian, James Peyer, may direct the voting and disposition of the shares held by Cambrian, subject in certain instances to the approval of Cambrian's Board of Directors. Mr. Peyer disclaims beneficial ownership of such shares.</footnote>
    </footnotes>

    <remarks>The Chief Executive Officer of Cambrian, James Peyer, may direct the voting and disposition of the shares held by Cambrian, subject in certain instances to the approval of Cambrian's Board of Directors.  James Peyer is also a director of the Issuer, and Cambrian may be deemed to be a director of the Issuer by deputization of James Peyer.</remarks>

    <ownerSignature>
        <signatureName>Cambrian BioPharma Inc, by: /s/ James Peyer</signatureName>
        <signatureDate>2023-08-02</signatureDate>
    </ownerSignature>
</ownershipDocument>
