Artikel ; Online: CAR-T cells targeting IL-1RAP produced in a closed semiautomatic system are ready for the first phase I clinical investigation in humans.
Current research in translational medicine
2023 Band 71, Heft 2, Seite(n) 103385
Abstract: Purpose of the study: The use of chimeric antigen receptor (CAR)-T cells has demonstrated excellent results in B-lymphoid malignancies. The Advanced Therapy Medicinal Products (ATMP) status and good manufacturing practice (GMP) of CAR-T cells require ... ...
| Abstract | Purpose of the study: The use of chimeric antigen receptor (CAR)-T cells has demonstrated excellent results in B-lymphoid malignancies. The Advanced Therapy Medicinal Products (ATMP) status and good manufacturing practice (GMP) of CAR-T cells require particular conditions of production performed in a pharmaceutical establishment. Our team developed a new medical drug candidate for acute myeloid leukemia (AML), a CAR targeting interleukin-1 receptor accessory protein (IL-1RAP) expressed by leukemia stem cells, which will need to be evaluated in a phase I-IIa clinical trial. During the preclinical development phase, we produced IL-1RAP CAR-T cells in a semi-automated closed system (CliniMACSࣨ Prodigy) using research grade lentiviral particles. Patients and the methods: The purpose of this work was to validate our production process and to characterize our preclinical GMP-like medicinal product. IL-1RAP CAR-T cells were produced from healthy donors in 9 days, either in an semi-automated closed system (with GMP-like compliant conditions) or according to another research protocols, which was used as a reference. Results: Based on phenotypic, functional and metabolic analyses, we were able to show that the final product is ready for clinical use. Finally, in a xenograft AML murine model, we demonstrated that the IL-1RAP CAR-T cells generated in a GMP-like environment could eliminate tumor cells and increase overall survival. Conclusion: We demonstrated that our IL-1RAP CAR-T cell preclinical GMP-like production process meets standard regulatory requirements in terms of CAR-T cell number, subpopulation phenotype and cytotoxic functionality. Our CAR-T cell production process was validated and can be used to produce medicinal IL-1RAP CAR-T cells for the first phase I clinical trial. |
|---|---|
| Mesh-Begriff(e) | Humans ; Animals ; Mice ; Immunotherapy, Adoptive/methods ; Interleukin-1 Receptor Accessory Protein/metabolism ; T-Lymphocytes/metabolism ; Phenotype |
| Chemische Substanzen | Interleukin-1 Receptor Accessory Protein |
| Sprache | Englisch |
| Erscheinungsdatum | 2023-02-04 |
| Erscheinungsland | France |
| Dokumenttyp | Journal Article |
| ISSN | 2452-3186 |
| ISSN (online) | 2452-3186 |
| DOI | 10.1016/j.retram.2023.103385 |
| Datenquelle | MEDical Literature Analysis and Retrieval System OnLINE |
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