AboutInVivoPlusanti-mousePD-1(CD279)

TheJ43monoclonalantibodyreactswithmousePD-1(programmeddeath-1)alsoknownasCD279.PD-1isa50-55kDacellsurfacereceptorencodedbythePdcd1genethatbelongstotheCD28familyoftheimmunoglobulinsuperfamily.PD-1istransientlyexpressedonCD4andCD8thymocytesaswellasactivatedTandBlymphocytesandmyeloidcells.PD-1expressiondeclinesaftersuccessfuleliminationofantigen.Additionally,Pdcd1mRNAisexpressedindevelopingBlymphocytesduringthepro-B-cellstage.PD-1’sstructureincludesaITIM(immunoreceptortyrosine-basedinhibitorymotif)suggestingthatPD-1negativelyregulatesTCRsignals.PD-1signalsviabindingitstwoligands,PD-L1andPD-L2bothmembersoftheB7family.Uponligandbinding,PD-1signalinginhibitsT-cellactivation,leADIngtoreducedproliferation,cytokineproduction,andT-celldeath.Additionally,PD-1isknowntoplaykeyrolesinperipheraltoleranceandpreventionofautoimmunediseaseinmiceasPD-1knockoutanimalsshowdilatedcardiomyopathy,splenomegaly,andlossofperipheraltolerance.InducedPD-L1expressioniscommoninmanytumorsincludingsquamouscellcarcinoma,colonadenocarcinoma,andbreastadenocarcinoma.PD-L1overexpressionresultsinincreasedresistanceoftumorcellstoCD8Tcellmediatedlysis.Inmousemodelsofmelanoma,tumorgrowthcanbetransientlyarrestedviatreatmentwithantibodieswhichblocktheinteractionbetweenPD-L1anditsreceptorPD-1.Forthesereasonsanti-PD-1mediatedimmunotherapiesarecurrentlybeingexploredascancertreatments.TheJ43antibodyhasbeenshowntoblockthebindingofbothmousePD-L1-IgandmousePD-L2-IgtoPD-1.