A Review of CAR T Cells and Adoptive T-Cell Therapies in Lymphoid and Solid Organ Malignancies

Abstract

Chimeric antigen receptor (CAR) T cells are genetically engineered T lymphocytes that express a synthetic receptor that recognizes a tumor cell surface antigen, which causes the T lymphocyte to kill the tumor cell. As of December 2024, the US Food and Drug Administration (FDA) approved six CAR T-cell therapies, with ten CAR T-cell therapies commercially available globally, which target the CD19 and B-cell maturation antigen (BCMA) molecules and with approved indications that include B-cell acute lymphoblastic leukemia (ALL), large B-cell lymphoma (LBCL), follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia (CLL), and multiple myeloma. Pharmaceutical and economic forecasts have shown that the global CAR T-cell therapy market was worth USD 4.6 billion in 2024, with a projected USD 25 billion by 2035. However, there are several challenges in treating hematologic malignancies with CAR T-cell therapy, which include reduced treatment efficacy and durability in some patients, acute and long-term adverse effects, lack of effective salvage treatments, limited access to CAR T-cell therapies due to cost and availability, and the rare association with developing myeloid malignancies. A tumor-infiltrating lymphocyte (TIL) therapy, lifileucel, is FDA-approved for advanced melanoma. The T-cell receptor (TCR) therapy, afamitresgene autoleucel, is FDA-approved for advanced synovial sarcoma. The results from ongoing studies and clinical trials are awaited in solid tumors (melanoma, sarcomas, and carcinomas). This article reviews recent developments and ongoing challenges in adoptive T-cell therapies, including CAR T-cell therapies, in lymphoid and solid organ malignancies.