Aleksandrova, Krasimira and Leise, Jana and Priesner, Christoph and Aktas, Murat and Apel, Michael and Assenmacher, Mario and Buerger, Iris and Richter, Anne and Altefrohne, Pia and Schubert, Christine and Holzinger, Astrid and Barden, Markus and Bezler, Valerie and von Bergwelt-Baildon, Michael and Borchmann, Peter and Goudeva, Lilia and Glienke, Wolfgang and Arseniev, Lubomir and Esser, Ruth and Abken, Hinrich and Koehl, Ulrike (2024) °Automated manufacturing and characterization of clinical grade autologous CD20 CAR T cells for the treatment of patients with stage III/IV melanoma. FRONTIERS IN IMMUNOLOGY, 15: 1328368. ISSN 1664-3224,
Full text not available from this repository. (Request a copy)Abstract
Introduction: Point-of-care (POC) manufacturing of chimeric antigen receptor (CAR) modified T cell has expanded rapidly over the last decade. In addition to the use of CD19 CAR T cells for hematological diseases, there is a growing interest in targeting a variety of tumor-associated epitopes. Methods: Here, we report the manufacturing and characterization of autologous anti-CD20 CAR T cells from melanoma patients within phase I clinical trial (NCT03893019). Using a second-generation lentiviral vector for the production of the CD20 CAR T cells on the CliniMACS Prodigy (R). Results: We demonstrated consistency in cell composition and functionality of the products manufactured at two different production sites. The T cell purity was >98.5%, a CD4/CD8 ratio between 2.5 and 5.5 and transduction rate between 34% and 61% on day 12 (harvest). Median expansion rate was 53-fold (range, 42-65-fold) with 1.7-3.8x109 CAR T cells at harvest, a sufficient number for the planned dose escalation steps (1x10(5)/kg, 1x10(6)/kg, 1x10(7)/kg BW). Complementary research of some of the products pointed out that the CAR+ cells expressed mainly central memory T-cell phenotype. All tested CAR T cell products were capable to translate into T cell activation upon engagement of CAR target cells, indicated by the increase in pro-inflammatory cytokine release and by the increase in CAR T cell amplification. Notably, there were some interindividual, cell-intrinsic differences at the level of cytokine release and amplification. CAR-mediated T cell activation depended on the level of CAR cognate antigen. Discussion: In conclusion, the CliniMACS Prodigy (R) platform is well suited for decentralized POC manufacturing of anti-CD20 CAR T cells and may be likewise applicable for the rapid and automated manufacturing of CAR T cells directed against other targets.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | OPEN-LABEL; METASTATIC MELANOMA; MINOR SUBSET; NIVOLUMAB; SURVIVAL; PHASE-3; MULTICENTER; IPILIMUMAB; REGRESSION; clinical CD20 CAR T cell trial; automated manufacturing of engineered T cell products; ex vivo expansion; cell composition of CAR T cell products; CD20 CAR investigational medicinal product |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 Jan 2026 09:27 |
| Last Modified: | 13 Jan 2026 09:27 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64815 |
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