Chimeric Antigen Receptor CAR)-Specic Monoclonal Antibody to Detect CD19-Specic T Cells in Clinical Trials.docVIP

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Chimeric Antigen Receptor CAR)-Specic Monoclonal Antibody to Detect CD19-Specic T Cells in Clinical Trials.doc

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Chimeric Antigen Receptor CAR)-Specic Monoclonal Antibody to Detect CD19-Specic T Cells in Clinical Trials

ChimericAntigenReceptor(CAR)-SpecificMonoclonal AntibodytoDetectCD19-SpecificTCellsinClinicalTrials BipulenduJena1,SourindraMaiti1,HelenHuls1,HarjeetSingh1,DeanA.Lee1,2,RichardE.Champlin3, LaurenceJ.N.Cooper1,2 * 1Division ofPediatrics, TheUniversity ofTexasMDAnderson Cancer Center,Houston,Texas, United States ofAmerica, 2TheUniversityofTexas Graduate School of BiomedicalSciences,Houston,Texas,UnitedStatesofAmerica,3DepartmentofStemCellTransplantationandCellularTherapy,TheUniversityofTexasMDAnderson CancerCenter,Houston,Texas,UnitedStatesofAmerica Abstract ClinicaltrialstargetingCD19onB-cellmalignanciesareunderwaywithencouraginganti-tumorresponses.MostinfuseT cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of aCD19-specificmousemonoclonalantibody(mAb,cloneFMC63).Wedescribeanovelanti-idiotypemonoclonalantibody + (mAb) to detect CD19-specific CAR T cells before and after their adoptive transfer. This mouse mAb was generated by immunizingwithacellularvaccineexpressingtheantigen-recognitiondomainofFMC63.ThespecificityofthemAb(clone + no.136.20.1)wasconfinedtothescFvregionoftheCARasvalidatedbyinhibitingCAR-dependentlysisofCD19 tumor targets.ThisclonecanbeusedtodetectCD19-specificCAR Tcellsinperipheralbloodmononuclearcellsatasensitivityof + 1:1,000.Inclinical settingsthemAb isused toinformon theimmunophenotype andpersistenceof administeredCD19- specificTcells.Thus,ourCD19-specificCARmAb(cloneno.136.20.1)willbeusefultoinvestigatorsimplementingCD19- specificCAR TcellstotreatB-lineagemalignancies.ThemethodologydescribedtodevelopaCAR-specificanti-idiotypic + mAbcouldbeextendedtoothergenetherapytrialstargetingdifferenttumorassociatedantigensinthecontextofCAR- basedadoptiveT-celltherapy. Citation:JenaB,MaitiS,HulsH,SinghH,LeeDA,etal.(2013)ChimericAntigenReceptor(CAR)-SpecificMonoclonalAntibodytoDetectCD19-SpecificTCellsin ClinicalTrials.PLoSONE8(3):e57838.doi:10.1371/journal.pone.005783