Point-of-care manufacturing of anti-CD19 CAR-T cells using a closed production platform: Experiences of an academic in Thailand

• Published in: Molecular Therapy: Oncology 2024-12, Vol.32 (4), p.200889, Article 200889
• Main Authors: Luanpitpong, Sudjit, Klaihmon, Phatchanat, Janan, Montira, Kungwankiattichai, Smith, Owattanapanich, Weerapat, Kunacheewa, Chutima, Chanthateyanonth, Supasorn, Donsakul, Nawapotch, U-pratya, Yaowalak, Warindpong, Thanatphak, Kittivorapart, Janejira, Permpikul, Parichart, Issaragrisil, Surapol
• Format: Article
• Language: English
• Subjects: automated; B cell malignancies; CAR; CAR-T cells; CD19; chimeric antigen receptor; manufacturing; MT: Regular Issue; Original; POC; point-of-care; Thailand
• ISSN: 2950-3299; 2950-3299
• DOI: 10.1016/j.omton.2024.200889

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. [Display omitted] Luanpitpong and colleagues present the manufacturing of non-commercial, clinical-grade anti-CD19 CAR-T cells with stringent quality control systems at the point of care in Thailand, which holds great promise for improving patient access to the therapy. They also shared their manufacturing experiences, which may help reduce the chance of manufacturing failure.