Scalable Production of <100 CAR-T Doses Using a 2 L Perfusion Stirred-Tank Bioreactor with Automated Harvest

• Autologous CAR-T therapies have transformed treatment outcomes in hematologic malignancies but remain limited by complex, patient-specific manufacturing, long production timelines, and high per-dose costs driven by variable starting material and multistep handling. These constraints restrict scalability, affordability, and broad patient access.
• Allogeneic, off-the-shelf CAR-T therapies aim to overcome these barriers by enabling large batch manufacturing, immediate treatment availability, and simplified logistics using engineered healthy donor T cells. Realizing this potential, however, requires intensified, scalable, and cost-efficient manufacturing workflows capable of producing hundreds of consistent, high-quality doses per batch. Although stirred-tank bioreactors (STRs) are widely established in large-scale biologics production, their application to multi-litre CAR-T manufacturing remains limited.
• To address these gaps, a serum-free, perfusion-intensified CAR-T expansion process was evaluated in a 2 L STR with a predictive 250 mL scale-down model, in-line capacitance monitoring, and automated downstream processing.