PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Ursch, L.T.* ; Müschen, J.S.* ; Ritter, J.* ; Klermund, J.* ; Bernard, B.E.* ; Kolb, S.* ; Warmuth, L.* ; Andrieux, G.* ; Miller, G. ; Jiménez-Muñoz, M. ; Theis, F.J. ; Boerries, M.* ; Busch, D.H.* ; Cathomen, T.* ; Schumann, K.*

Modulation of TCR stimulation and pifithrin-α improves the genomic safety profile of CRISPR-engineered human T cells.

Cell Rep. Med. 5:101846 (2024)
Verlagsversion DOI PMC
Closed
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
CRISPR-engineered chimeric antigen receptor (CAR) T cells are at the forefront of novel cancer treatments. However, several reports describe the occurrence of CRISPR-induced chromosomal aberrations. So far, measures to increase the genomic safety of T cell products focused mainly on the components of the CRISPR-Cas9 system and less on T cell-intrinsic features, such as their massive expansion after T cell receptor (TCR) stimulation. Here, we describe driving forces of indel formation in primary human T cells. Increased T cell activation and proliferation speed correlate with larger deletions. Editing of non-activated T cells reduces the risk of large deletions with the downside of reduced knockout efficiencies. Alternatively, the addition of the small-molecule pifithrin-α limits large deletions, chromosomal translocations, and aneuploidy in a p53-independent manner while maintaining the functionality of CRISPR-engineered T cells, including CAR T cells. Controlling T cell activation and pifithrin-α treatment are easily implementable strategies to improve the genomic integrity of CRISPR-engineered T cells.
Impact Factor
Scopus SNIP
Altmetric
11.700
0.000
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Car T Cell Therapy ; Crispr Engineering ; T Cell Activation ; Aneuploidy ; Chromosomal Aberrations ; Genomic Integrity ; Human T cells ; Large Deletions ; Pifithrin-alpha ; Translocations; Protects Mice; P53; Inhibitor; Targets; Alpha; Dna; Apoptosis
Sprache englisch
Veröffentlichungsjahr 2024
HGF-Berichtsjahr 2024
ISSN (print) / ISBN 2666-3791
e-ISSN 2666-3791
Zeitschrift Cell Reports Medicine
Quellenangaben Band: 5, Heft: 12, Seiten: , Artikelnummer: 101846 Supplement: ,
Verlag Cell Press
Verlagsort 50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Begutachtungsstatus Peer reviewed
Institut(e) CF Statistical Consulting (CF-STATCON)
Institute of Computational Biology (ICB)
POF Topic(s) 30505 - New Technologies for Biomedical Discoveries
30205 - Bioengineering and Digital Health
Forschungsfeld(er) Enabling and Novel Technologies
PSP-Element(e) A-632200-001
G-503800-001
Förderungen
Else Kroner-Fresenius-Stiftung
Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)
German Federal Ministry of Education and Research (BMBF) within the Medical Informatics Funding Scheme
Core Facility "CyTUM MIH"in cell sorting (DFG)
DOI 10.1016/j.xcrm.2024.101846
WOS ID 001390942800001
Scopus ID 85211974676
PubMed ID 39637860
Erfassungsdatum 2024-12-10
[➜Korrektur melden]