Adoptive transfer of syngeneic T cells transduced with a chimeric antigen receptor that recognizes murine CD19 can eradicate lymphoma and normal B cells.
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.
Kochenderfer
James N
JN
Surgery Branch of the National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. kochendj@mail.nih.gov
Yu
Zhiya
Z
Frasheri
Dorina
D
Restifo
Nicholas P
NP
Rosenberg
Steven A
SA
D019264:Adoptive Transfer; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D020014:K562 Cells; D016393:Lymphoma, B-Cell / Q000276:immunology* / Q000628:therapy*; D051379:Mice; D008809:Mice, Inbred C3H; D011948:Receptors, Antigen, T-Cell / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014161:Transduction, Genetic
D018941:Antigens, CD19; D011948:Receptors, Antigen, T-Cell; D011993:Recombinant Fusion Proteins