Are we there yet? The road to faster and more efficient CAR T cell manufacturing

Abstract Chimeric antigen receptor (CAR) T cell therapies have achieved clinical success in autologous treatment of hematological malignancies. However, their broader application remains limited. Beyond the biological challenges associated with the immunosuppressive microenvironment of solid tumors and the graft-versus-host disease risks inherent to allogeneic settings, the widespread adoption of CAR T cells is hindered by the high costs, long and complex vein-to-vein timelines and variability in product quality. Rapid CAR T cell manufacturing has emerged as an alternative paradigm that prioritizes shortened production workflows and preservation of naïve and stem-like T cell phenotypes with superior in vivo expansion, persistence and anti-tumor efficacy. This review examines rapid CAR T cell manufacturing from a bioprocess engineering perspective, focusing on how critical process parameters can be explored to shape CAR T cell phenotype and function within shortened timelines. We highlight key technological enablers, including automation, microfluidic systems, process analytical technologies, artificial intelligence-driven bioprocess control, quality control methodologies as well as safety considerations unique to accelerated workflows. Emerging CAR T cell manufacturing models, such as point-of-care production and in vivo CAR T cells generation, are also discussed. These insights outline engineering strategies to enable faster, more consistent and clinically effective CAR T cells.