CAR-T Cell Therapy: Historical Development, Current Applications, and Future Perspectives

The major forms of cancer immunotherapy include checkpoint blockade, therapeutic antibodies, vaccines, oncolytic viruses, and adoptive cell therapy.Adoptive approaches are unusual because the administered product consists of viable immune cells that may expand after infusion and remain capable of long-term surveillance.Clinical experience with tumor-infiltrating lymphocytes and T-cell receptor (TCR)-engineered lymphocytes estab-Chimeric antigen receptor (CAR)-T cell therapy redirects T lymphocytes by introducing a synthetic receptor that couples antibody-like antigen binding to intracellular T-cell signaling.Because CARs recognize intact surface molecules, engineered cells can attack selected targets without peptide presentation by major histocompatibility complex molecules.This review outlines the immunological basis of the approach, the development of successive receptor generations, established clinical uses, and emerging strategies intended to broaden efficacy and access.The addition of costimulatory signaling converted early proofof-concept receptors into clinically effective second-generation products.CD19-directed therapies have achieved durable disease control in several B-cell leukemias and lymphomas, while B-cell maturation antigen-directed products have established CAR-T therapy in multiple myeloma.In contrast, most solid tumors remain difficult to treat because target expression is heterogeneous, trafficking is inefficient, and the tumor microenvironment suppresses T-cell function.Current innovation therefore extends beyond receptor architecture to multi-antigen recognition, controllable signaling, armored constructs, donorderived products, shortened manufacturing, and direct in vivo T-cell programming.Early clinical evidence that CAR-T cells can be generated in patients suggests that treatment delivery may eventually become faster and more scalable.Continued progress will require designs that balance potency, persistence, safety, manufacturability, and equitable access.