Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells

Blood. 2010 Nov 11;116(19):3875-86. doi: 10.1182/blood-2010-01-265041. Epub 2010 Jul 14.

Abstract

Adoptive T-cell therapy with anti-CD19 chimeric antigen receptor (CAR)-expressing T cells is a new approach for treating advanced B-cell malignancies. To evaluate anti-CD19-CAR-transduced T cells in a murine model of adoptive T-cell therapy, we developed a CAR that specifically recognized murine CD19. We used T cells that were retrovirally transduced with this CAR to treat mice bearing a syngeneic lymphoma that naturally expressed the self-antigen murine CD19. One infusion of anti-CD19-CAR-transduced T cells completely eliminated normal B cells from mice for at least 143 days. Anti-CD19-CAR-transduced T cells eradicated intraperitoneally injected lymphoma cells and large subcutaneous lymphoma masses. The antilymphoma efficacy of anti-CD19-CAR-transduced T cells was critically dependent on irradiation of mice before anti-CD19-CAR-transduced T-cell infusion. Anti-CD19-CAR-transduced T cells had superior antilymphoma efficacy compared with the anti-CD19 monoclonal antibody from which the anti-CD19 CAR was derived. Our results demonstrated impressive antilymphoma activity and profound destruction of normal B cells caused by anti-CD19-CAR-transduced T cells in a clinically relevant murine model.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, CD19 / metabolism*
  • B-Lymphocytes / immunology*
  • Cell Line, Tumor
  • Female
  • Humans
  • K562 Cells
  • Lymphoma, B-Cell / immunology*
  • Lymphoma, B-Cell / therapy*
  • Mice
  • Mice, Inbred C3H
  • Receptors, Antigen, T-Cell / genetics
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • T-Lymphocytes / immunology*
  • Transduction, Genetic

Substances

  • Antigens, CD19
  • Receptors, Antigen, T-Cell
  • Recombinant Fusion Proteins