Production and characterization of haploidentical CD19 CAR T cells: Validated to induce a continuous complete remission in a patient with relapsed refractory B-cell ALL.

Autor: Prasongtanakij S; Office of Research, Academic Affairs and Innovation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Anurathapan U; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Vanichapol T; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Jittorntrum B; Office of Research, Academic Affairs and Innovation, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Atjanasuppat K; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Pongpitcha P; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Pakakasama S; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Songdej D; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Sirachainan N; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Paisooksantivatana K; Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand., Borwaornpinyo S; Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok, Thailand., Andersson BS; Department of Stem Cell Transplantation, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA., Hongeng S; Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
Jazyk: angličtina
Zdroj: Asia-Pacific journal of clinical oncology [Asia Pac J Clin Oncol] 2022 Feb; Vol. 18 (1), pp. 44-51. Date of Electronic Publication: 2020 Sep 24.
DOI: 10.1111/ajco.13474
Abstrakt: Aims: The purpose of this study was to design and manufacture CD19 chimeric antigen receptor (CAR)-modified T cells for clinical use in Thailand, as a model for how this technology can be directly applied at individual institutions treating high-risk leukemia patients.
Methods: We constructed second-generation CAR T cells expressing CD19 scFV-CD28-CD3ζ with different lengths of the spacer region: full, intermediate, and short length, by using a lentiviral vector. We wanted to determine whether the difference in length of the spacer would affect the cytotoxic potential of the CD19 CAR T cells against the leukemic cells.
Results: We found that all constructs of CD19 CAR T cells exhibited a similar level of cytotoxicity against several human lymphoma and leukemia cell lines. For the clinical application, we chose the intermediate length spacer construct CD19 CAR T cells, hypothesizing that the highest transduction efficiency coupled with a slower initial proliferation in vitro might lead to effective leukemic cell kill, yet a lower probability for serious clinical side effects. We then tested the clinical efficacy of our CD19 CAR T cells in one patient with refractory/relapsed acute B-cell lymphoblastic leukemia. This patient indeed had minimal clinical side effects after the CAR T-cell infusion, and he remains in an unmaintained, ongoing complete remission 10+ months after his T-cell treatment.
Conclusion: Our CD19 CAR T cells demonstrated efficacies in acute lymphoblastic B-cell leukemia, and will be used to establish an immunotherapeutic program for high-risk B-cell acute lymphoblastic leukemia in Thailand. We propose that this approach can be used as a model for how this new exciting technology can be applied directly at individual institutions that treat (a large number of) patients with high-risk leukemia.
(© 2020 John Wiley & Sons Australia, Ltd.)
Databáze: MEDLINE
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