CAR-T cell therapy in lymphomas.

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapy has profoundly transformed the therapeutic landscape of B cell lymphomas, particularly in relapsed and refractory settings. Built upon decades of advances in immunology, molecular biology, and gene therapy, CAR T cells enable major histocompatibility complex–independent tumor recognition and potent antitumor immune responses. This review summarizes the historical development of CAR-T therapy, key aspects of manufacturing and quality control, approved indications, clinical outcomes, treatment related toxicities, and emerging innovations in the field. Second generation anti CD19 CAR T products have demonstrated unprecedented response rates and durable remissions across multiple subtypes of B cell non Hodgkin lymphomas, including diffuse large B cell lymphoma, follicular lymphoma, and mantle cell lymphoma, leading to regulatory approvals in several disease settings and earlier lines of therapy. Despite these successes, CAR T therapy remains associated with unique toxicities such as cytokine release syndrome, immune effector cell–associated neurotoxicity, prolonged cytopenias, and infectious complications, requiring specialized multidisciplinary management. Rapid advances in CAR T engineering and manufacturing are now addressing key biological and logistical limitations. Innovations such as ultra rapid manufacturing platforms, dual targeted CAR constructs, and allogeneic “off the shelf ” products aim to improve cellular fitness, reduce antigen escape, enhance accessibility, and shorten vein to vein time. As CAR T therapy continues to evolve toward earlier disease settings and broader global implementation, coordinated efforts in regulatory frameworks, infrastructure development, toxicity management, and sustainable financing will be essential to maximize its impact on patient outcomes.