This project is evaluating a novel fully-human anti-CD19 CAR. The rationale for a fully-human CAR is to avoid recipient anti-CAR immune responses that probably target most CARs in current clinical use because most CARs contain murine components. The new fully-human CAR was invented by James Kochenderfer, and all preclinical work on this CAR was performed in his laboratory. This project is a combination of a clinical trial of infusions of autologous anti-CD19 chimeric-antigen-receptor-transduced T cells and laboratory experiments performed on cells obtained from patients that received infusions of the chimeric-antigen-receptor-transduced T cells. We have initiated a new clinical trial in the past year that The most prominent toxicity were hypotension and neurological toxicity. These results demonstrate that CAR-expressing T cells can specifically eliminate targeted cells and cause significant cytokine-mediated toxicity in humans. Current efforts are aimed at evaluating low-dose chemotherapy regimens administered before anti-CD19 CAR T cells. We initiated a clinical trial of autologous T cells expressing this novel fully-human CAR in January of 2016. We have treated 9 patients to date. Seven patients are evaluable for response, and 6 of the 7 patients have had objective anti-lymphoma responses.
