CHIMERIC ANTIGEN RECEPTOR T-CELL THERAPY - NARRATIVE REVIEW ON MECHANISMS, CLINICAL APPLICATIONS, ADVERSE EFFECTS, SUPPORTIVE CARE, AND FUTURE DIRECTIONS

Cancer remains one of the leading causes of morbidity and mortality worldwide despite continuous advances in diagnosis and treatment. Conventional treatment modalities, including surgery, chemotherapy, radiotherapy, and targeted therapies, have significantly improved survival in many malignancies. However, treatment resistance, disease relapse, and therapy-related toxicities continue to limit long-term clinical outcomes. These challenges have driven the development of immunotherapeutic approaches that harness the body's immune system to recognize and eliminate malignant cells.
Among the available immunotherapies, chimeric antigen receptor T-cell (CAR-T) therapy has emerged as one of the most important advances in cancer treatment. CAR-T therapy involves the genetic modification of autologous or allogeneic T lymphocytes to express synthetic receptors capable of recognizing tumor-associated antigens independently of major histocompatibility complex (MHC) presentation. Following reinfusion, these engineered cells selectively target tumor cells, proliferate, release inflammatory cytokines, and induce tumor cell death through multiple cytotoxic mechanisms.
CAR-T therapy has produced remarkable clinical responses in patients with relapsed or refractory hematological malignancies. Currently approved indications include B-cell acute lymphoblastic leukemia, diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, follicular lymphoma, and multiple myeloma. In addition, several clinical trials are evaluating its potential role in other hematological cancers and solid tumors.
Despite its impressive therapeutic efficacy, CAR-T therapy is associated with important limitations, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, prolonged cytopenias, infections, manufacturing complexity, high treatment costs, and reduced effectiveness against solid tumors.⁵˒⁹˒¹³˒²¹ Ongoing research is focused on improving CAR design, developing allogeneic and gene-edited CAR-T products, optimizing manufacturing strategies, and exploring combination therapies to enhance efficacy while minimizing toxicity.²⁵˒²⁶˒²⁷˒²⁸
This narrative review summarizes the evolution of CAR-T cell therapy, its structural components, mechanism of action, manufacturing process, approved clinical indications, adverse effects, supportive care strategies, current challenges, and emerging future directions. ²˒⁷˒²⁸