Perfusion microbioreactor for CAR-Treg manufacturing.

Manufacturing cell and gene therapies (CGTs) at scale presents challenges in cost, product consistency, and adaptability to personalized treatments. Traditional large-volume bioreactors are designed to support cell growth through controlled nutrient delivery and gas exchange, but are poorly suited to the decentralized, small-batch production required for personalized therapies such as chimeric antigen receptor (CAR) T cells. To address this, we have developed the KCL-Microbioreactor (K-MBR), a closed microbioreactor platform based on microfluidic principles. Engineered in polydimethylsiloxane (PDMS), the K-MBR combines spatial confinement, semi-continuous perfusion, and integrated viral transduction in a compact footprint, enabling efficient gene delivery and robust expansion of therapeutic cells. We demonstrate the platform's utility by generating functional CAR-Tregs targeting HLA-A2, achieving a 92% increase in yield compared to conventional methods. The K-MBR offers a streamlined solution for CGT manufacturing, with potential to reduce production costs and enhance scalability across a broad range of cell therapies.