High-Density Microfluidic Bioreactor Optimizes CAR T Cell Production

Researchers from the Singapore-MIT Alliance for Research and Technology (SMART) have developed a novel method for producing clinical doses of chimeric antigen receptor (CAR)-T cells using a microfluidic chip. This novel approach could transform the scaling of manufacturing of autologous cell therapies, making it more efficient and affordable.

The team successfully manufactured and expanded CAR-T cells in a two-milliliter automated closed-system microbioreactor, producing over 60 million cells from lymphoma donors and over 200 million from healthy donors. These cells were as effective as those produced using conventional methods but required less space, fewer resources, and shorter production times.

"This new method suggests that a dramatic miniaturization of current-generation autologous cell therapy production is feasible, with the potential of significantly alleviating manufacturing limitations of CAR-T cell therapy," said Wei-Xiang Sin, first author of the study published in Nature Biomedical Engineering.

The microbioreactor's small size and high efficiency could lead to significant reductions in reagent costs and potentially enable point-of-care manufacturing outside of laboratory settings. This advancement could benefit patients, especially pediatric cases with low T cell numbers. 

"This advancement in cell therapy manufacturing could ultimately offer a point-of-care platform that could substantially increase the number of CAR-T cell production slots, reducing the wait times and cost of goods of these living medicines—making cell therapy more accessible to the masses,” explained senior author Michael Birnbaum.

The team is now working on further optimizing the process and developing systems to enable bedside manufacturing of CAR-T cells.