Chimeric Antigen Receptor Therapy For Hematologic Malignancies

Chimeric antigen receptor (CAR) T-cells are genetically engineered cells that represent a novel class of cancer immunotherapy. In general, the process of autologous CAR T-cell therapy begins with harvesting white blood cells from the patient via leukapheresis followed by T-cell receptor activation and genetic engineering via retroviral or lentiviral transduction. After the CAR T-cells are generated, they are expanded to clinically relevant numbers, undergo quality control testing, and are cryopreserved. Commercial CAR T-cell products are manufactured at a centralized facility, necessitating transfer of the apheresis product to the manufacturing site, and the final cryopreserved CAR T-cell product back to the treatment facility. Typically, the patient undergoes lymphodepleting chemotherapy to create a favorable immune environment for CAR T-cell activity prior to receiving a single intravenous infusion of the product. Multiple commercial CAR T-cell products have been approved by the U.S. Food and Drug Administration for the treatment of lymphoma and leukemia. Tisagenlecleucel and brexucabtagene autoleucel are approved for treatment of subsets of patients with leukemia and lymphoma and axicabtagene ciloleucel and lisocabtagene maraleucel are approved to treat subsets of patients with lymphoma.