Functionality and Cell Senescence of CD4/ CD8-Selected CD20 CAR T Cells Manufactured Using the Automated CliniMACS Prodigy® Platform
| Autor: | Lilia Goudeva, Fanni Kubaink, Jana Leise, Wolfgang Glienke, Andrew Kaiser, Hinrich Abken, Mike Essl, Ruth Esser, Andreas Hombach, Marion Jurk, Lubomir Arseniev, Murat Aktas, Krasimira Aleksandrova, Ulrike Köhl, Georg Rauser, Iris Bürger, Christoph Priesner, Anette Melk |
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| Přispěvatelé: | Publica |
| Rok vydání: | 2018 |
| Předmět: |
CD4 / CD8 selection
Cell 030204 cardiovascular system & hematology GMP manufacturing of CAR Tcells CD19 Andrology 03 medical and health sciences 0302 clinical medicine medicine Immunology and Allergy Cytotoxic T cell ddc:610 B cell CD20 Telomere length chimeric antigen receptor biology Hematology Leukapheresis Chimeric antigen receptor GMP manufacturing of CAR T cells CD4/CD8 selection Telomere length Cytotoxicity Telomere medicine.anatomical_structure biology.protein cytotoxicity CD8 030215 immunology Research Article |
| Zdroj: | Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie. 46(1) |
| ISSN: | 1660-3796 |
| Popis: | 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® 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-γ 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. |
| Databáze: | OpenAIRE |
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