PuSH - Publication Server of Helmholtz Zentrum München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Gottschlich, A.* ; Thomas, M. ; Grünmeier, R.* ; Lesch, S.* ; Rohrbacher, L.* ; Igl, V.* ; Briukhovetska, D.* ; Benmebarek, M.R.* ; Vick, B. ; Dede, S.* ; Müller, K.* ; Xu, T.* ; Dhoqina, D.* ; Märkl, F.* ; Robinson, S.* ; Sendelhofert, A.* ; Schulz, H.* ; Umut, * ; Kavaka, V.* ; Tsiverioti, C.A.* ; Carlini, E.* ; Nandi, S.* ; Strzalkowski, T.* ; Lorenzini, T.* ; Stock, S.* ; Müller, P.J.* ; Dörr, J.* ; Seifert, M.* ; Cadilha, B.L.* ; Brabenec, R. ; Röder, N.* ; Rataj, F.* ; Nüesch, M.* ; Modemann, F.* ; Wellbrock, J.* ; Fiedler, W.* ; Kellner, C.* ; Beltran, E.* ; Herold, T.* ; Paquet, D.* ; Jeremias, I. ; von Baumgarten, L.* ; Endres, S. ; Subklewe, M.* ; Marr, C. ; Kobold, S.

Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia.

Nat. Biotechnol. 41, 1618-1632 (2023)
Postprint DOI PMC
Open Access Green
Chimeric antigen receptor T cells (CAR-T cells) have emerged as a powerful treatment option for individuals with B cell malignancies but have yet to achieve success in treating acute myeloid leukemia (AML) due to a lack of safe targets. Here we leveraged an atlas of publicly available RNA-sequencing data of over 500,000 single cells from 15 individuals with AML and tissue from 9 healthy individuals for prediction of target antigens that are expressed on malignant cells but lacking on healthy cells, including T cells. Aided by this high-resolution, single-cell expression approach, we computationally identify colony-stimulating factor 1 receptor and cluster of differentiation 86 as targets for CAR-T cell therapy in AML. Functional validation of these established CAR-T cells shows robust in vitro and in vivo efficacy in cell line- and human-derived AML models with minimal off-target toxicity toward relevant healthy human tissues. This provides a strong rationale for further clinical development.
Impact Factor
Scopus SNIP
Web of Science
Times Cited
Altmetric
46.900
0.000
11
Tags
Annotations
Special Publikation
Hide on homepage

Edit extra information
Edit own tags
Private
Edit own annotation
Private
Hide on publication lists
on hompage
Mark as special
publikation
Publication type Article: Journal article
Document type Scientific Article
Keywords Costimulatory Molecules; Blood Monocytes; Expression; Therapy; Cd86; Identification; Inhibition; Target; Tissue; Gene
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 1087-0156
e-ISSN 1546-1696
Journal Nature Biotechnology
Quellenangaben Volume: 41, Issue: 11, Pages: 1618-1632 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place New York, NY
Reviewing status Peer reviewed
Institute(s) Unit for Clinical Pharmacology (KKG-EKLiP)
Institute of AI for Health (AIH)
Research Unit Apoptosis in Hematopoietic Stem Cells (AHS)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30205 - Bioengineering and Digital Health
30204 - Cell Programming and Repair
Research field(s) Immune Response and Infection
Enabling and Novel Technologies
Stem Cell and Neuroscience
PSP Element(s) G-522100-001
G-540007-001
G-506600-001
Grants Bundesministerium fur Bildung und Forschung
m4-Award of the Bavarian Ministry for Economical Affairs
Go-Bio-Initiative
Institutional Strategy LMUexcellent of LMU Munich (within the framework of the German Excellence Initiative)
Ernst Jung Stiftung
Wilhelm-Sander-Stiftung
German Cancer Aid
Forderprogramm fur Forschung und Lehre der Medizinischen Fakultat der LMU
Marie Sklodowska-Curie Training Network for Optimizing Adoptive T Cell Therapy of Cancer - Horizon 2020 program of the European Union
Marie Sklodowska-Curie Training Network for the Immunotherapy of Cancer (IMMUTRAIN) - Horizon 2020 program of the European Union
Melanoma Research Alliance
international doctoral program 'i-Target: immunotargeting of cancer' - Elite Network of Bavaria
Deutsche Forschungsgemeinschaft (DFG)
Bavarian Cancer Research Center
Else Kroner-Fresenius-Stiftung
Marie Curie Actions (MSCA)

DFG (German Research Foundation)
European Research Council under the European Union's Horizon 2020 research and innovation program
DKTK School of Oncology
Munich Clinician Scientist Program
Else Kroner-Fresenius Clinician Scientist Program Cancer Immunotherapy
European Research Council
Alzheimer's Association
DFG (German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology
Hector Foundation
Bayerische Forschungsstiftung (BAYCELLator)
Deutsche Jose Carreras Leukamie Stiftung
Fritz-Bender Foundation
DFG
Volkswagen Foundation
DOI 10.1038/s41587-023-01684-0
WOS ID 000958280000003
PubMed ID 36914885
Erfassungsdatum 2023-10-06
[➜Report correction]