Universität zu Köln

Aleksandrova, Krasimira, Leise, Jana, Priesner, Christoph, Melk, Anette, Kubaink, Fanni, Abken, Hinrich, Hombach, Andreas, Aktas, Murat, Essl, Mike, Buerger, Iris, Kaiser, Andrew, Rauser, Georg, Jurk, Marion, Goudeva, Lilia, Glienke, Wolfgang, Arseniev, Lubomir, 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. Transfus. Med. Hemother., 46 (1). S. 47 - 55. BASEL: KARGER. ISSN 1660-3818

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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:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Aleksandrova, Krasimira UNSPECIFIED UNSPECIFIED UNSPECIFIED Leise, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Priesner, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED Melk, Anette UNSPECIFIED UNSPECIFIED UNSPECIFIED Kubaink, Fanni UNSPECIFIED UNSPECIFIED UNSPECIFIED Abken, Hinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Hombach, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Aktas, Murat UNSPECIFIED UNSPECIFIED UNSPECIFIED Essl, Mike UNSPECIFIED UNSPECIFIED UNSPECIFIED Buerger, Iris UNSPECIFIED UNSPECIFIED UNSPECIFIED Kaiser, Andrew UNSPECIFIED UNSPECIFIED UNSPECIFIED Rauser, Georg UNSPECIFIED UNSPECIFIED UNSPECIFIED Jurk, Marion UNSPECIFIED UNSPECIFIED UNSPECIFIED Goudeva, Lilia UNSPECIFIED UNSPECIFIED UNSPECIFIED Glienke, Wolfgang UNSPECIFIED UNSPECIFIED UNSPECIFIED Arseniev, Lubomir UNSPECIFIED UNSPECIFIED UNSPECIFIED Esser, Ruth UNSPECIFIED UNSPECIFIED UNSPECIFIED Koehl, Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-139389
DOI:	10.1159/000495772
Journal or Publication Title:	Transfus. Med. Hemother.
Volume:	46
Number:	1
Page Range:	S. 47 - 55
Date:	2019
Publisher:	KARGER
Place of Publication:	BASEL
ISSN:	1660-3818
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CHIMERIC ANTIGEN RECEPTOR; ADOPTIVE IMMUNOTHERAPY; THERAPY Multiple languages Hematology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13938