Supplementary file 1_The future directions of CAR-T Cell therapy: unlocking the potential of immunotherapy in cancer treatment.docx

Emerging approaches to overcoming antigen loss, including γδ CAR-T cells, are reviewed alongside their current limitations, including restricted ex vivo expansion, donor variability, isolation challenges, and uncertain long-term persistence. The review also addresses the growing importance of improving affordability and accessibility through allogeneic “off-the-shelf” CAR-T products, genome editing technologies, automated manufacturing platforms, and rational combination therapies designed to enhance efficacy while reducing treatment costs.

In addition, advances in toxicity prediction are evaluated, focusing on biomarkers beyond interleukin-6, including ferritin, C-reactive protein, soluble interleukin-2 receptor alpha, and multiparametric cytokine signatures for the early identification of severe cytokine release syndrome. Collectively, these developments demonstrate that future progress in CAR-T cell therapy will depend not only on enhancing antitumour efficacy but also on improving safety, accessibility, manufacturing efficiency, and equitable global implementation through evidence-based innovation.</p>