Chen and Lipschitz et al. used immunostaining and in situ hybridization to analyze large B cell lymphoma biopsies from patients treated with autologous CAR T cells expressing a second generation (CD3ζ and CD28) anti-CD19 scFv. PD-1+CD8+ T cells were increased in responsive patients’ specimens taken >5 days post infusion. CAR T cells were the minority of intratumoral T cells, and most CAR and non-CAR T cells expressed Ki67, IFNγ, granzyme B and/or PD-1, and markers of current/past activation. In biopsies with CAR T cells, activated non-CAR T and other immune cells were present at 5-10 fold higher levels and were the sole source of IL-6 in almost all samples.
Contributed by Paula Hochman
ABSTRACT: The mechanisms of CAR-T cell mediated anti-tumor immunity and toxicity remain poorly characterized due to few studies examining the intact tumor microenvironment (TME) following CAR T-cell infusion. Axicabtagene ciloleucel is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for patients with large B-cell lymphoma. We devised multiplex immunostaining and in-situ hybridization assays to interrogate CAR T cells and other immune cell infiltrates in biopsies of diffuse large B-cell lymphoma following axicabtagene ciloleucel infusion. We found a majority of intratumoral CAR T cells expressed markers of T-cell activation but, unexpectedly, comprised
Author Info: (1) Center for Immuno-Oncology, Dana Farber Cancer Institute, Boston, United States of America. (2) Center for Immuno-Oncology, Dana Farber Cancer Institute, Boston, United States
Author Info: (1) Center for Immuno-Oncology, Dana Farber Cancer Institute, Boston, United States of America. (2) Center for Immuno-Oncology, Dana Farber Cancer Institute, Boston, United States of America. (3) Center for Immuno-Oncology, Dana Farber Cancer Institute, Boston, United States of America. (4) Department of Medical Oncology, Dana Farber Cancer Institute, Boston, United States of America. (5) Department of Medical Oncology, Dana Farber Cancer Institute, Boston, United States of America. (6) Department of Pathology, Brigham & Women's Hospital, Boston, United States of America. (7) Department of Medical Oncology, Dana Farber Cancer Institute, Boston, United States of America. (8) Kite, A Gilead Company, Santa Monica, United States of America. (9) Kite, A Gilead Company, Santa Monica, United States of America. (10) Kite, A Gilead Company, Santa Monica, United States of America. (11) Kite, A Gilead Company, Santa Monica, United States of America. (12) Kite, A Gilead Company, Santa Monica, United States of America. (13) Department of Pathology, Brigham & Women's Hospital, Boston, United States of America.
