Aleksandrova, Krasimira and Leise, Jana and Priesner, Christoph and Melk, Anette and Kubaink, Fanni and Abken, Hinrich and Hombach, Andreas and Aktas, Murat and Essl, Mike and Buerger, Iris and Kaiser, Andrew and Rauser, Georg and Jurk, Marion and Goudeva, Lilia and Glienke, Wolfgang and Arseniev, Lubomir and Esser, Ruth and Koehl, Ulrike (2019) Functionality and Cell Senescence of CD4/CD8-Selected CD20 CAR T Cells Manufactured Using the Automated CliniMACS Prodigy (R) Platform. TRANSFUSION MEDICINE AND HEMOTHERAPY, 46 (1). pp. 47-54. ISSN 1660-3796, 1660-3818
Full text not available from this repository.Abstract
Clinical studies using autologous CAR T cells have achieved spectacular remissions in refractory CD19+ B cell leukaemia, however some of the patient treatments with CAR T cells failed. Beside the heterogeneity of leukaemia, the distribution and senescence of the autologous cells from heavily pretreated patients might be further reasons for this. We performed six consecutive large-scale manufacturing processes for CD20 CAR T cells from healthy donor leukapheresis using the automated CliniMACS Prodigy (R) platform. Starting with a CD4/CD8-positive selection, a high purity of a median of 97% T cells with a median 65-fold cell expansion was achieved. Interestingly, the transduction rate was significantly higher for CD4+compared to CD8+ T cells and reached in a median of 23%. CD20 CAR T cells showed a good specific IFN-gamma secretion after cocultivation with CD20+ target cells which correlated with good cytotoxic activity. Most importantly, 3 out of 5 CAR T cell products showed an increase in telomere length during the manufacturing process, while telomere length remained consistent in one and decreased in another process. In conclusion, this shows for the first time that beside heterogeneity among healthy donors, CAR T cell products also differ regarding cell senescence, even for cells manufactured in a standardised automated process. (C) 2019 S. Karger AG, Basel
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CHIMERIC ANTIGEN RECEPTOR; ADOPTIVE IMMUNOTHERAPY; THERAPY; Chimeric antigen receptor; GMP manufacturing of CAR T cells; CD4/CD8 selection; Telomere length; Cytotoxicity |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Zentren des Universitätsklinikums Regensburg > Regensburger Centrum für Interventionelle Immunologie (RCI) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 21 Apr 2020 11:59 |
| Last Modified: | 21 Apr 2020 11:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27839 |
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