Expanding CAR-T cell immunotherapy horizons through microfluidics.

Chimeric antigen receptor (CAR)-T cell therapies have revolutionized cancer treatment, particularly in hematological malignancies. However, their application to solid tumors is limited, and they face challenges in safety, scalability, and cost. To enhance current CAR-T cell therapies, the integration of microfluidic technologies, harnessing their inherent advantages, such as reduced sample consumption, simplicity in operation, cost-effectiveness, automation, and high scalability, has emerged as a powerful solution. This review provides a comprehensive overview of the step-by-step manufacturing process of CAR-T cells, identifies existing difficulties at each production stage, and discusses the successful implementation of microfluidics and related technologies in addressing these challenges. Furthermore, this review investigates the potential of microfluidics-based methodologies in advancing cell-based therapy across various applications, including solid tumors, next-generation CAR constructs, T-cell receptors, and the development of allogeneic "off-the-shelf" CAR products.