Cell Therapy Innovations for Liquid and Solid Tumors and their Clinical Translation

Recent studies have highlighted the complex interplay between CAR T cells and the tumor microenvironment (TME) in B cell lymphomas. Our studies demonstrate that CAR T cell-derived interferon-gamma (IFN-γ) induces inducible nitric oxide synthase (iNOS) expression in tumor-associated macrophages (TAMs), leading to CAR T cell dysfunction through metabolic disruption and activation of apoptotic pathways. IFN-γ also modulates the Th1/Th17 axis and CAR T toxicities.  These findings underscore the significance of the TME in CAR T cell therapy resistance and point towards potential strategies, such as targeting iNOS or modulating Th1/Th17 responses, to enhance therapeutic efficacy in B cell lymphomas.

Dr. Marco Davila is a physician-scientist that manages patients with cancer but spends the majority of his effort on T cell therapy research. He trained at the Center for Cell Engineering at the Memorial Sloan Kettering Cancer Center (MSKCC) where he was responsible for the development and clinical application of CD19-targeted chimeric antigen receptor (CAR) T cell therapy. He worked at the interface of the laboratory, GMP Cell Therapy Facility (GMP-CTF), and clinic, which provided him a broadly encompassing perspective of this young field. His team’s work contributed to what has become the first gene-engineered T cell therapy for cancer approved by a regulatory agency. He then transitioned to the H. Lee Moffitt Cancer Center to establish a translational T cell therapy research program and have directed the successful awarded (or in process of awarding) four IND’s of cellular therapies for hematologic malignancies. He recently moved to the Roswell Park Cancer Center where he serves as the Associate Cancer Center Director and Senior Vice President for Translational Research. He directly oversees the GMP- vector and cell therapy facilities, as well as clinical faculty and staff to facilitate rapid translation of cell therapies for the patients. He remains involved in laboratory research, clinical research, and management of patients treated with standard and experimental cell therapies including CAR T cells, TCR-transgenic T cells, and tumor-infiltrating lymphocytes. His team’s Transplant and Cell Therapy (TCT) clinical service is highly productive. In the past 12 months they have performed greater than 200 cell therapy infusions into patients. He directs the useful interface of the lab, GMP-CTF, and clinic, which will facilitate the clinical translation and improvement of cell therapies for patients.