SPOTLIGHT Since 2017, five additional CAR T-cell therapies have been approved by FDA, all for the treatment of blood cancers, including NHL, leukemia, and most recently, multiple myeloma (see Sidebar 40, p. 117). Collectively, these treatments have transformed the lives of adult and pediatric patients with blood cancers (455). As one example, based on a recent analysis, axicabtagene ciloleucel (Yescarta), which was also approved by FDA in 2017, is the first treatment in nearly three decades to improve overall survival in relapsed or refractory large B-cell lymphoma (456). Generating CAR T cells is a complex procedure that can only be performed at specially certified health care facilities by highly trained medical professionals. Additionally, like other cancer treatments, CAR T-cell therapies can cause side effects, some of which can be potentially life-threatening. Another issue that researchers are trying to address is the fact that CAR T-cell therapies have so far proven less successful against solid tumors. Developing simpler and safer ways to bring the promise of this class of immunotherapeutics to more patients with different cancer types is an area of active research (see On the Horizon for Immunotherapy, p. 128). T Cell-based Adoptive Cell Therapy Adoptive T cell therapy, also called cellular immunotherapy, dramatically increases the number of cancer-killing immune T cells, thus boosting a patient’s immune system to seek and destroy cancer cells. It is a complex and multistep medical procedure. During the treatment, T cells are harvested from the patient to expand them in number and/or genetically modify them in the laboratory to enhance their cancer-fighting capabilities. The expanded and/or genetically enhanced T cells are then reinfused in the patient to help eliminate cancer cells. TYPES OF ADOPTIVE T-CELL THERAPY There are three main types of adoptive T-cell therapy. As of July 31, 2023, only one type, chimeric antigen receptor (CAR) T-cell therapy, has been approved by the U.S. Food and Drug Administration. Chimeric antigen receptor (CAR) T-cell therapy T cells are harvested from a patient’s blood and genetically modified in the laboratory so that they have a synthetic protein called a CAR on their surface that recognizes and binds to a specific protein on the surface of the patient’s cancer cells. The genetically modified T cells are expanded in number and infused back into the patient. The CAR modification helps the T cells directly bind to and eradicate the patient’s cancer cells. T-cell receptor (TCR) T-cell therapy T cells are harvested from a patient’s blood and genetically modified in the laboratory so that they have a synthetic protein called TCR on their surface, which recognizes certain protein fragments on the surface of the patient’s cancer cells. The genetically modified T cells are expanded in number and infused back into the patient. The TCR modification helps the T cells seek out the patient’s cancer cells more effectively and triggers them to attack the patient’s cancer cells. Tumor-infiltrating lymphocyte (TIL) therapy T cells are harvested directly from a patient’s tumor, expanded in number in the laboratory, and infused back into the patient. Many of these T cells naturally recognize and kill the patient’s cancer cells. SIDEBAR 39 1992 IL-2 approved to treat aggressive form of kidney cancer (460) 1998 IL-2 approved to treat metastatic melanoma (461) INTERLEUKIN-2 (IL-2) AACR Cancer Progress Report 2023 Immunotherapy: Pushing the Frontier of Cancer Medicine 116
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