title: Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials.
abstract: Clinical trials targeting CD19 on B-cell malignancies are underway with encouraging anti-tumor responses. Most infuse T cells genetically modified to express a chimeric antigen receptor (CAR) with specificity derived from the scFv region of a CD19-specific mouse monoclonal antibody (mAb, clone FMC63). We describe a novel anti-idiotype monoclonal antibody (mAb) to detect CD19-specific CAR(+) T cells before and after their adoptive transfer. This mouse mAb was generated by immunizing with a cellular vaccine expressing the antigen-recognition domain of FMC63. The specificity of the mAb (clone no. 136.20.1) was confined to the scFv region of the CAR as validated by inhibiting CAR-dependent lysis of CD19(+) tumor targets. This clone can be used to detect CD19-specific CAR(+) T cells in peripheral blood mononuclear cells at a sensitivity of 1∶1,000. In clinical settings the mAb is used to inform on the immunophenotype and persistence of administered CD19-specific T cells. Thus, our CD19-specific CAR mAb (clone no. 136.20.1) will be useful to investigators implementing CD19-specific CAR(+) T cells to treat B-lineage malignancies. The methodology described to develop a CAR-specific anti-idiotypic mAb could be extended to other gene therapy trials targeting different tumor associated antigens in the context of CAR-based adoptive T-cell therapy.
authors.affiliation: Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
authors.forename: Bipulendu
authors.initials: B
authors.lastname: Jena
authors.forename: Sourindra
authors.initials: S
authors.lastname: Maiti
authors.forename: Helen
authors.initials: H
authors.lastname: Huls
authors.forename: Harjeet
authors.initials: H
authors.lastname: Singh
authors.forename: Dean A
authors.initials: DA
authors.lastname: Lee
authors.forename: Richard E
authors.initials: RE
authors.lastname: Champlin
authors.forename: Laurence J N
authors.initials: LJ
authors.lastname: Cooper
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000918:Antibody Specificity; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D002986:Clinical Trials as Topic; D006801:Humans; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000628:therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D050506:Mutant Chimeric Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D057127:Single-Chain Antibodies / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000637:transplantation
chemical_list: D000911:Antibodies, Monoclonal; D018941:Antigens, CD19; D050506:Mutant Chimeric Proteins; D011948:Receptors, Antigen, T-Cell; D057127:Single-Chain Antibodies