Disrupting the Solid Tumor Environment Using CAR T Therapies
Available to view On Demand
Two FDA-approved immunotherapies for cancers of the blood have ushered in a new era in the development of gene and cell therapies.
The drugs, Yescarta (axicabtagene ciloleucel) and Kymriah (tisagenlecleucel), both comprise patient T cells that have been genetically engineered to express an artificial T cell receptor called a chimeric antigen receptor (CAR). These CARs are designed to recognize CD19 antigen on the blood tumor cells, which allows the CAR-expressing T cell to target them for destruction. Previous clinical trials testing these agents showed striking effects in patients, leading to high rates of remission and, in many cases, complete recovery.
Efforts are now underway to exploit CAR T and related adoptive cell immunotherapy technology (ACT) to treat solid tumors—tumors which have so far proven largely resistant to treatment with these agents. Our immune system detects and destroys abnormal cells, including tumors.
Patients whose tumors harbor tumor-infiltrating lymphocytes (TILs) often fare better than those whose tumors do not. However, most patients lack a significant tumor-reactive immune infiltrate, and the tumor environment itself can be inherently immunosuppressive.
Moreover, identification of tumor-specific antigens that can be safely and selectively targeted has been a challenge.
In this Cell Press webinar, Prasad Adusumilli, Stephen Gottschalk, and Leonid Metelitsa discuss the challenges of targeting CAR T and related ACT platforms to the solid tumor environment, and they provide examples of how combining gene and cell therapy with checkpoint inhibition and other strategies may enable us to disrupt the tumor environment and its dynamic response to such therapies.
Deupty Chief and Attending, Thoracic Surgery; Vice Chair, Department of Surgery; Head, Solid Tumors Cell Therapy; Cellular Therapeutics Center Director, Mesothelioma Program; Memorial Sloan-Kettering Cancer Center, NY
Co-director, Neuroblastoma Program; Professor, Department of Pediatrics, Section of Hematology/Oncology; Baylor College of Medicine
Chair, Department of Bone Marrow Transplantation and Cellular Therapy; Endowed Chair in Bone Marrow Transplantation and Cellular Therapy; Member St. Jude Faculty