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

Autor:	Luanpitpong S; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Siriraj Cell Factory for Cancer Immunotherapy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Blood Products and Cellular Immunotherapy Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Klaihmon P; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Siriraj Cell Factory for Cancer Immunotherapy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Janan M; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Siriraj Cell Factory for Cancer Immunotherapy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Blood Products and Cellular Immunotherapy Research Group, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Kungwankiattichai S; Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Center of Excellence of Siriraj Adult Acute Myeloid/Lymphoblastic Leukemia, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Owattanapanich W; Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Center of Excellence of Siriraj Adult Acute Myeloid/Lymphoblastic Leukemia, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Kunacheewa C; Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Center of Excellence of Siriraj Adult Acute Myeloid/Lymphoblastic Leukemia, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Chanthateyanonth S; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Siriraj Cell Factory for Cancer Immunotherapy, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Donsakul N; Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Center of Excellence of Siriraj Adult Acute Myeloid/Lymphoblastic Leukemia, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., U-Pratya Y; Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Warindpong T; Department of Transfusion Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Kittivorapart J; Department of Transfusion Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Permpikul P; Department of Transfusion Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand., Issaragrisil S; Siriraj Center of Excellence for Stem Cell Research, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; Division of Hematology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.; BDMS Center of Excellence for Hematology, Wattanosoth Cancer Hospital, Bangkok 10310, Thailand.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Oncology [Mol Ther Oncol] 2024 Oct 05; Vol. 32 (4), pp. 200889. Date of Electronic Publication: 2024 Oct 05 (Print Publication: 2024).
DOI:	10.1016/j.omton.2024.200889
Abstrakt:	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. Competing Interests: All authors declare no competing interests. The research was conducted in the absence of any commercial, proprietary, or financial relationships that could be construed as a potential conflict of interest. All authors and their immediate family members have not been affiliated or associated with Miltenyi Biotec or any other related companies. (© 2024 The Author(s).)
Databáze:	MEDLINE
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