使用封闭生产平台即时制备抗 CD19 CAR-T 细胞：泰国某学术机构的经验

Anti-CD19 chimeric antigen receptor (CAR)-T cell therapy has evolved as a standard of care for various forms of relapsed/refractory B cell malignancies in major developed countries.

However, access to industry-driven CAR-T cell therapy is limited in developing countries, partly due to the centralized manufacturing system.

Here, we demonstrated the feasibility of the point-of-care (POC) manufacturing of anti-CD19 CAR-T cells from heavily pretreated patients and healthy graft donors at an academic medical center in Thailand using a closed semi-automated production platform, CliniMACS Prodigy, and established in-process quality control and release testing to ensure their identity, purity, sterility, safety, and potency. Nine out of the nine products manufactured were used in a pilot study (ISRCTN17901467).

However, we did observe that starting T cells with CD4/CD8 ratios of less than one-third had a high chance of manufacturing failure, which could be minimized by serum supplementation.

Further analysis of T cell phenotypes in the infused versus circulating CAR-T cells revealed the differentiation from early memory subtypes toward effector cells in vivo . The POC manufacturing and quality control settings herein could be applied to other CAR-T cell products and may benefit other academics, especially those in developing countries, making CAR-T cells more accessible.