Recruiting Cytotoxic T Cells to Folate-Receptor-Positive Cancer Cells

《Recruiting Cytotoxic T Cells to Folate-Receptor-Positive Cancer Cells》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、AngewandteChemieDOI:10.1002/anie.201306866CancerImmunotherapyHotPaperRecruitingCytotoxicTCellstoFolate-Receptor-PositiveCancerCells**SumithA.Kularatne,VishalDeshmukh,MarcoGymnopoulos,SandraL.Biroc,JinmingXia,ShailajaSrinagesh,YingSun,NingZou,MarkShimazu,JasonPinkstaff,S

2、emsiEnsari,NickKnudsen,AnthonyManibusan,JunY.Axup,ChanHyukKim,VaughnV.Smider,TsotneJavahishvili,andPeterG.Schultz*+OnenewclassofbiologicsthatisgeneratingagreatdealofbispecificantibodythattargetscytotoxicTcellstoHer2interestasnext-generationcancertherapeuticsarebispecifi

3、cbreastcancercellsshowedgoodhalf-lifeandexcellent[10]antibodiesthatsimultaneouslytargettheclusterofdiffer-efficacyinrodentxenograftmodels.Inadditiontoanti-entiation3(CD3)proteinandtumor-associatedantigenstobodies,small-moleculeligandshavebeenidentifiedwithhighrecruitcyt

4、otoxicTcellsfromthepatientsownimmuneaffinityandspecificityfortumor-associatedcell-surfaceanti-[1][11,12]systemtoeliminatecancercells.Examplesincludethefirstgens.Oneexampleisfolicacid(FA),whichbindstightly[2]approvedbispecificantibodyinEurope,Catumaxomab,andtothefolater

5、eceptor(FR)andishighlyexpressedon[2][13]Blinatumomab,ananti-CD19-anti-CD3bispecificantibodyavarietyofcancerandinflammatorycells.BasedonthethatshowedahighrateofcompleteresponseinrefractorylimiteddistributionofFRinhealthytissues,Lowandco-acutelymphoblasticleukemia(ALL)pat

6、ientsinphaseIIworkershaveusedfolatefortheselectivedeliveryofanti-[3,4]+clinicaltrials.Ascancertherapeutics,bispecificantibodiesneoplasticagentstoFRcancers,suchasovariancancerand[14]haveseveralattractivefeatures:formationofanimmuno-non-small-celllungcancer,andtheseagents

7、areshowinglogicalsynapseresultsinefficientkillingoftumorcellsbypromisingclinicalresults.AlthoughfourisoformsofFRhaveactivatedTcells;Tcell-mediatedcytotoxicitycanhavebeenreported(FRa,FRb,FRg,andFRd),onlyFRaandFRbabystandereffectonheterogeneoustumorandcancerstemareoverexp

8、ressedinepithelial-derivedcancers(i.e.,ovary,cells;bispecificantibodiesshouldbeeffectiveagainstcancerskidney,b