Advancements and expanding applications of CAR-T cell therapy.

CAR T-cell therapy has become a transformative modality in oncology, demonstrating sustained clinical efficacy in hematologic malignancies. Recent investigations have expanded its potential beyond cancer to immune-mediated disorders, including autoimmune diseases such as multiple sclerosis and systemic lupus erythematosus, as well as chronic viral infections including HIV and hepatitis B. This review examines the mechanistic foundations of CAR-T cells, advances in universal and allogeneic engineering strategies designed to mitigate graft-versus-host disease and host rejection, and emerging in vivo gene-delivery platforms that aim to bypass conventional ex vivo manufacturing. We further evaluate safety-control architectures, including logic-gated and inducible systems, and discuss translational barriers related to scalability, manufacturing standardization, and long-term immune durability. While technological innovations in genome editing, synthetic biology, and computational design continue to refine CAR-T platforms, substantial biological and logistical challenges remain. A critical synthesis of these evolving strategies is necessary to distinguish incremental optimization from paradigm-shifting advances and to define the future trajectory of CAR-based immunotherapy across oncology and immune-mediated diseases.