Six CAR-T-cell therapies have been approved by the European Commission and the US FDA, and other T-cell therapies are being developed.
Chimeric antigen receptor (CAR)-T cells and T-cell therapies have been used in the treatment of various cancers for several years. In a review published in JAMA, a research team led by Christian Hinrichs, MD, of the Rutgers Cancer Institute of New Brunswick, New Jersey, summarizes the current understanding of cellular immunotherapies in cancer treatment. CAR-T cells are genetically modified T cells that express a synthetic receptor designed to recognize a surface protein found on tumor cells. Tumor-infiltrating lymphocytes (TILs) are natural T cells that are cultured ex vivo from resected tumor tissue. T-cell receptor (TCR)-T cells are genetically altered T cells that express a natural T-cell receptor targeting a cellular protein. Hinrichs is one of the developers of TIL therapy and TCR treatment for human papillomavirus-associated cancers. CAR-T-Cell Therapies At present, six CAR-T-cell therapies have been approved by the European Commission and the US Food and Drug Administration (FDA). The CAR-T-cell products targeting CD19 are axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, and tisagenlecleucel. They are used for: B-cell non-Hodgkin lymphoma Acute lymphoblastic B-cell leukemia Chronic lymphocytic leukemia Tisagenlecleucel is also approved for use in children and young adults with acute lymphoblastic B-cell leukemia. The CAR-T-cell therapies targeting B-cell maturation antigen — ciltacabtagene autoleucel and idecabtagene vicleucel — are indicated for multiple myeloma. Challenges in treating hematologic diseases with CAR-T cells include acute and long-term side effects, limited effectiveness and duration of effect, the lack of effective salvage therapies, long wait times, and often restricted access to these therapies. Side Effects Anti-CD19 CAR-T cells can expand rapidly in the recipient, causing significant increases in proinflammatory cytokines such as interleukin-6 or interferon-gamma. This can trigger a cytokine…