دورية أكاديمية
Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia.
| العنوان: | Single-cell transcriptomic atlas-guided development of CAR-T cells for the treatment of acute myeloid leukemia. |
|---|---|
| المؤلفون: | Gottschlich A; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.; Bavarian Cancer Research Center (BZKF), Munich, Germany.; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany., Thomas M; Institute of AI for Health, Helmholtz Munich, Neuherberg, Germany.; School of Life Sciences Weihenstephan, Technical University of Munich, Freising, Germany., Grünmeier R; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Lesch S; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Rohrbacher L; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; Laboratory for Translational Cancer Immunology, Gene Center, LMU Munich, Munich, Germany., Igl V; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Briukhovetska D; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Benmebarek MR; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Vick B; Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Munich, German Research Center for Environmental Health (HMGU), Munich, Germany.; Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany., Dede S; Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Müller K; Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Xu T; Department of Neurology, University Hospital, LMU Munich, Munich, Germany., Dhoqina D; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Märkl F; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Robinson S; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Sendelhofert A; Institute of Pathology, LMU Munich, Munich, Germany., Schulz H; Institute of Pathology, LMU Munich, Munich, Germany., Umut Ö; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Kavaka V; Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Martinsried, Germany., Tsiverioti CA; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Carlini E; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Nandi S; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Strzalkowski T; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Lorenzini T; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Stock S; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany., Müller PJ; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Dörr J; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Seifert M; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Cadilha BL; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Brabenec R; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.; Institute of AI for Health, Helmholtz Munich, Neuherberg, Germany., Röder N; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Rataj F; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Nüesch M; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany., Modemann F; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.; Mildred Scheel Cancer Career Center, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf Hamburg, Hamburg, Germany., Wellbrock J; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Fiedler W; Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald University Cancer Center, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Kellner C; Division of Transfusion Medicine, Cell Therapeutics and Haemostaseology, University Hospital, LMU Munich, Munich, Germany., Beltrán E; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.; Institute of Clinical Neuroimmunology, University Hospital, LMU Munich, Munich, Germany.; Biomedical Center (BMC), Faculty of Medicine, LMU Munich, Martinsried, Germany., Herold T; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany., Paquet D; Institute for Stroke and Dementia Research (ISD), University Hospital, LMU Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Jeremias I; Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Munich, German Research Center for Environmental Health (HMGU), Munich, Germany.; Department of Pediatrics, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany., von Baumgarten L; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; Department of Neurosurgery, LMU Munich, Munich, Germany., Endres S; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Munich, Research Center for Environmental Health (HMGU), Neuherberg, Germany., Subklewe M; Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; Laboratory for Translational Cancer Immunology, Gene Center, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany., Marr C; Institute of AI for Health, Helmholtz Munich, Neuherberg, Germany., Kobold S; Division of Clinical Pharmacology, University Hospital, LMU Munich, Member of the German Center for Lung Research (DZL), Munich, Germany. sebastian.kobold@med.uni-muenchen.de.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. sebastian.kobold@med.uni-muenchen.de.; Einheit für Klinische Pharmakologie (EKLiP), Helmholtz Munich, Research Center for Environmental Health (HMGU), Neuherberg, Germany. sebastian.kobold@med.uni-muenchen.de. |
| المصدر: | Nature biotechnology [Nat Biotechnol] 2023 Nov; Vol. 41 (11), pp. 1618-1632. Date of Electronic Publication: 2023 Mar 13. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Nature America Publishing Country of Publication: United States NLM ID: 9604648 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1546-1696 (Electronic) Linking ISSN: 10870156 NLM ISO Abbreviation: Nat Biotechnol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: New York Ny : Nature America Publishing Original Publication: New York, NY : Nature Pub. Co., [1996- |
| مواضيع طبية MeSH: | Transcriptome*/genetics , Leukemia, Myeloid, Acute*/genetics , Leukemia, Myeloid, Acute*/therapy , Leukemia, Myeloid, Acute*/metabolism, Humans ; T-Lymphocytes ; Immunotherapy, Adoptive ; Cell Line ; Cell Line, Tumor |
| مستخلص: | 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. (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.) |
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| معلومات مُعتمدة: | 756017 International ERC_ European Research Council |
| تواريخ الأحداث: | Date Created: 20230314 Date Completed: 20231113 Latest Revision: 20240304 |
| رمز التحديث: | 20240305 |
| مُعرف محوري في PubMed: | PMC7615296 |
| DOI: | 10.1038/s41587-023-01684-0 |
| PMID: | 36914885 |
| قاعدة البيانات: | MEDLINE |
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| DOI: | 10.1038/s41587-023-01684-0 |