Dr. Adusumilli on the Rationale for Mesothelin-Targeted CAR T-Cell Therapy

Prasad S. Adusumilli, MD, surgeon, deputy chief of Thoracic Service, co-director of the Mesothelioma Program, head of Solid Tumors Cell Therapy, Cellular Therapeutics Center, at Memorial Sloan Kettering Cancer Center, discusses the rationale for an autologous mesothelin-targeted CAR T-cell therapy in advanced solid tumors.

Surface antigens, such as CD19, are more easily targeted in hematologic malignancies than they are in solid tumors, explains Adusumilli. Prior to the phase I study that investigated the use of an autologous mesothelin-targeted CAR T-cell therapy, investigators studied approximately 2,000 thoracic cancers and noticed that mesothelin is overexpressed in mesothelioma, lung cancer, triple-negative breast cancer, and pancreatic cancer.

Most importantly, investigators realized that mesothelin was partially responsible for the aggressiveness of the disease, making it unlikely that the cancer cell will shed the antigen under immune attack. They realized that if they were able to target mesothelin, approximately 2,000,000 patients could be treated in the United States alone, says Adusumilli. Moreover, they learned that by targeting mesothelin, they could target the tumor cells and spare the patient’s normal cells.