Next-generation CAR T therapy offers hope but faces clinical challenges

A new editorial perspective was published in Volume 17 of Oncotarget on February 20, 2026, titled "CAR-T therapy: Trailblazing CAR(ing) in cancer treatment."

Led by Uzma Saqib - with corresponding author Krishnan Hajela from the School of Life Sciences, Devi Ahilya Vishwavidyalaya - the perspective reviews recent clinical and translational advances in chimeric antigen receptor T-cell (CAR-T) therapy and highlights both its promise and its remaining barriers. The piece synthesizes recent clinical advances in hematologic malignancies and emerging applications in solid tumors, while focusing attention on safety (for example, cytokine release syndrome and neurotoxicity), resistance, antigen specificity, and access disparities.

The authors summarize the CAR-T workflow (leukapheresis → genetic modification and expansion → infusion) and note major recent clinical gains - including improved outcomes in leukemia, lymphoma, and multiple myeloma - that support wider adoption of cellular immunotherapy approaches. They emphasize that despite these advances, important clinical challenges remain, particularly for solid tumors, where antigen selection, tumor microenvironment, and T-cell trafficking limit efficacy. At the same time, the perspective highlights technological and clinical strategies under development to overcome these obstacles, including next-generation CAR designs and improved supportive-care protocols.

"Despite its promise, CAR T-cell therapy faces several critical challenges."

The authors call out clear next steps for the field: (1) continued refinement of CAR constructs (dual-targeting, switchable/on-off systems, armored CARs) to improve specificity and reduce on-target/off-tumor toxicity; (2) improved management protocols and prophylactic measures to mitigate CRS and neurotoxicity; (3) expanded investigation of allogeneic or alternative CAR-T platforms to address manufacturing, cost, and access barriers; and (4) focused translational studies to improve T-cell trafficking and efficacy in solid tumors. They also highlight equity issues - socioeconomic and racial disparities that limit access to CAR-T - and urge that broad deployment plans include strategies to expand availability and affordability.