Chimeric antigen receptor (CAR)-specific monoclonal antibody to detect CD19-specific T cells in clinical trials

PLoS One. 2013;8(3):e57838. doi: 10.1371/journal.pone.0057838. Epub 2013 Mar 1.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antibodies, Monoclonal / biosynthesis*
  • Antibodies, Monoclonal / genetics
  • Antibodies, Monoclonal / immunology
  • Antibody Specificity
  • Antigens, CD19 / genetics
  • Antigens, CD19 / immunology*
  • Clinical Trials as Topic
  • Humans
  • Lymphoma, B-Cell / immunology
  • Lymphoma, B-Cell / therapy
  • Mice
  • Mice, Inbred BALB C
  • Mutant Chimeric Proteins / analysis*
  • Mutant Chimeric Proteins / genetics
  • Mutant Chimeric Proteins / immunology
  • Receptors, Antigen, T-Cell / analysis*
  • Receptors, Antigen, T-Cell / genetics
  • Receptors, Antigen, T-Cell / immunology
  • Single-Chain Antibodies / biosynthesis*
  • Single-Chain Antibodies / genetics
  • Single-Chain Antibodies / immunology
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / transplantation

Substances

  • Antibodies, Monoclonal
  • Antigens, CD19
  • Mutant Chimeric Proteins
  • Receptors, Antigen, T-Cell
  • Single-Chain Antibodies