At the Bedside: Adoptive cell therapy for melanoma—clinical development

Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society

关键词: T cell;    immunotherapy;    IL‐;    2;    lymphoid depletion;    T cell receptor;   

DOI  :  10.1189/jlb.0513293

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

Adoptivecelltherapyformelanoma,particularlyusingTIL,consistsofacomplexanddifficultsetofprocedures,althoughithasastrongpreclinicalbackgroundandjustificationandhasbeenpursuedclinicallybyonesmallgroupofinvestigatorsoverthelast20years.Morerecentdevelopmentsandabetterunderstandingofthemolecularbasisoftheanti‐tumorimmuneresponsehaveledtotheconductofclinicaltrialsthatuselymphoiddepletionwithchemotherapyand/orTBItoexploitthefavorableimmunemilieuofhomeostaticlymphoidreconstitutionduringtransferofeffectorTcells.ImprovedwaysofpropagatingTcellsexvivohavealsosimplifiedandshortenedthecell‐growthprocess.CurrentTILtrialshavenowbeenexpandedbeyondtheinitialcenterwhereitwasdeveloped,reproducingexcellentobjectiveresponseratesof40–50%inpreviouslytreatedmelanomapatientsandmoreimportantly,demonstratingthatasignificantproportionofpatientswillbealiveandfreeofdisease3–5yearsaftertreatment,raisingthepossibilitythatthosepatientsmaybecuredoftheirdisease.NewermethodsforgrowingtheinfiltratingTcellsusingimmune‐checkpointantibodiesorotheragentstoconditionthetumorbeforeharvestandimprovedtechnologytosimplifythecomplexandoftencumbersomecell‐growthprocesssuggestthatthistechnologymaybeabletobedisseminatedtoawideselectionofcancercentersandmaybeacandidatefortestinginarandomizedPhaseIIItrialtoshowdefinitivelyitsbenefitinpatientswithmetastaticmelanoma.Intheaccompanyingreview,thepreclinicalworkthatsupportstheideaofadoptivecelltherapywithTILandexpandstheconceptinpromisingnewwayswillbeexplored...

【 授权许可】

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