Universität zu Köln

Prinz, Lars Fabian ORCID: 0000-0002-3580-7627, Riet, Tobias ORCID: 0000-0002-8211-7071, Neureuther, Daniel Felix, Lennartz, Simon ORCID: 0000-0001-7202-398X, Chrobok, Danuta, Hübbe, Hanna, Uhl, Gregor ORCID: 0000-0003-3792-1076, Riet, Nicole, Hofmann, Petra, Hösel, Marianna, Simon, Adrian Georg ORCID: 0000-0002-2709-863X, Tetenborg, Luis, Segbers, Paul, Shimono, Joji, Gödel, Philipp ORCID: 0000-0001-7887-8313, Balke-Want, Hyatt ORCID: 0000-0002-5963-7626, Flümann, Ruth ORCID: 0000-0002-7147-7557, Knittel, Gero, Reinhardt, Hans Christian, Scheid, Christoph ORCID: 0009-0007-6539-226X, Büttner, Reinhard ORCID: 0000-0001-8806-4786, Chapuy, Björn, Ullrich, Roland Tillmann, Hallek, Michael ORCID: 0000-0002-7425-4455 and Chmielewski, Markus Martin ORCID: 0000-0001-9348-5219 (2024). An anti-CD19/CTLA-4 switch improves efficacy and selectivity of CAR T cells targeting CD80/86-upregulated DLBCL. Cell Reports Medicine, 5 (2). pp. 1-26. Elsevier. ISSN 2666-3791

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Abstract

[Artikel-Nr.: 101421] Chimeric antigen receptor T cell (CAR T) therapy is a potent treatment for relapsed/refractory (r/r) B cell lymphomas but provides lasting remissions in only ∼40% of patients and is associated with serious adverse events. We identify an upregulation of CD80 and/or CD86 in tumor tissue of (r/r) diffuse large B cell lymphoma (DLBCL) patients treated with tisagenlecleucel. This finding leads to the development of the CAR/CCR (chimeric checkpoint receptor) design, which consists of a CD19-specific first-generation CAR co-expressed with a recombinant CTLA-4-linked receptor with a 4-1BB co-stimulatory domain. CAR/CCR T cells demonstrate superior efficacy in xenograft mouse models compared with CAR T cells, superior long-term activity, and superior selectivity in in vitro assays with non-malignant CD19+ cells. In addition, immunocompetent mice show an intact CD80−CD19+ B cell population after CAR/CCR T cell treatment. The results reveal the CAR/CCR design as a promising strategy for further translational study.

Item Type:	Article
Creators:	Creators Email ORCID ORCID Put Code Prinz, Lars Fabian UNSPECIFIED https://orcid.org/0000-0002-3580-7627 UNSPECIFIED Riet, Tobias UNSPECIFIED https://orcid.org/0000-0002-8211-7071 UNSPECIFIED Neureuther, Daniel Felix UNSPECIFIED UNSPECIFIED UNSPECIFIED Lennartz, Simon UNSPECIFIED https://orcid.org/0000-0001-7202-398X UNSPECIFIED Chrobok, Danuta UNSPECIFIED UNSPECIFIED UNSPECIFIED Hübbe, Hanna UNSPECIFIED UNSPECIFIED UNSPECIFIED Uhl, Gregor UNSPECIFIED https://orcid.org/0000-0003-3792-1076 UNSPECIFIED Riet, Nicole UNSPECIFIED UNSPECIFIED UNSPECIFIED Hofmann, Petra UNSPECIFIED UNSPECIFIED UNSPECIFIED Hösel, Marianna UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Adrian Georg UNSPECIFIED https://orcid.org/0000-0002-2709-863X UNSPECIFIED Tetenborg, Luis UNSPECIFIED UNSPECIFIED UNSPECIFIED Segbers, Paul UNSPECIFIED UNSPECIFIED UNSPECIFIED Shimono, Joji UNSPECIFIED UNSPECIFIED UNSPECIFIED Gödel, Philipp UNSPECIFIED https://orcid.org/0000-0001-7887-8313 UNSPECIFIED Balke-Want, Hyatt UNSPECIFIED https://orcid.org/0000-0002-5963-7626 UNSPECIFIED Flümann, Ruth UNSPECIFIED https://orcid.org/0000-0002-7147-7557 UNSPECIFIED Knittel, Gero UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinhardt, Hans Christian UNSPECIFIED UNSPECIFIED UNSPECIFIED Scheid, Christoph UNSPECIFIED https://orcid.org/0009-0007-6539-226X UNSPECIFIED Büttner, Reinhard UNSPECIFIED https://orcid.org/0000-0001-8806-4786 UNSPECIFIED Chapuy, Björn UNSPECIFIED UNSPECIFIED UNSPECIFIED Ullrich, Roland Tillmann UNSPECIFIED UNSPECIFIED UNSPECIFIED Hallek, Michael UNSPECIFIED https://orcid.org/0000-0002-7425-4455 UNSPECIFIED Chmielewski, Markus Martin UNSPECIFIED https://orcid.org/0000-0001-9348-5219 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-814018
Identification Number:	10.1016/j.xcrm.2024.101421
Journal or Publication Title:	Cell Reports Medicine
Volume:	5
Number:	2
Page Range:	pp. 1-26
Number of Pages:	26
Date:	20 February 2024
Publisher:	Elsevier
ISSN:	2666-3791
Language:	English
Faculty:	External institution Faculty of Medicine
Divisions:	Außeruniversitäre Forschungseinrichtungen > MPI for Biology of Ageing CECAD - Cluster of Excellence Cellular Stress Responses in Aging-Associated Diseases Faculty of Medicine > Innere Medizin > Klinik I für Innere Medizin - Hämatologie und Onkologie Faculty of Medicine > Pathologie und Neuropathologie > Institut für Pathologie Zentrum für Molekulare Medizin
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language CAR T cells ; lymphoma ; DLBCL ; FL ; checkpoint ligand ; chimeric checkpoint receptor ; neurotoxicity ; CD19 ; CD80 ; CD86 ; English
['eprint_fieldname_oa_funders' not defined]:	Publikationsfonds UzK
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/81401