Chimeric antigen receptor (CAR) T-cell therapies use genetically engineered T cells that mediate T-cell activation and costimulation.~1,2 CAR T-cell therapies can produce sustained remission in hematologic malignancies that are refractory to standard therapies.3 Tisagenlecleucel and axicabtagene ciloleucel are among the first CAR T-cell therapies approved by the US Food and Drug Administration (FDA) for the treatment of acute lymphoblastic leukemia and diffuse large B-cell lymphoma, respectively, and several other CAR T-cell therapies are on the horizon.~2,4,5 In addition to tisagenlecleucel and axicabtagene ciloleucel, currently available CAR T-cell therapies recently approved by the FDA include brexucabtagene autoleucel, idecabtagene vicleucel, and lisocabtagene maraleu-cel.~6-8 CAR T-cell therapies are designed to recognize and bind to specific antigens on tumor cells, leading to CAR T-cell activation and proliferation and eventually resulting in significant and durable destruction of malignant cells.~1. The design of CAR T-cell therapies is deliberate in targeting specific antigens on tumor cells. However, these therapies can potentially cause destruction of normal, nonmalignant cells when targeting a tumor-associated antigen also expressed on normal cells. Destruction of normal cells is referred to as an on-target, off-tumor effect.3 CD19, a B-cell-specific surface protein, is expressed throughout B-cell development and is present on a host of B-cell malignancies, including B-cell acute lymphoblastic leukemia, B-cell chronic lymphocytic leukemia, and B-cell non-Hodgkin lymphoma, among other B-cell malignancies. Therefore, CD 19 is a target of some CAR T-cell therapies. Another CAR T-cell therapy target is B-cell maturation antigen, which is expressed in multiple myeloma cells and is a target of idecabtagene vicleucel.~9
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