CRISPR/Cas9 editing of NKG2A improves the efficacy of primary CD33-directed chimeric antigen receptor natural killer cells.

Humans CRISPR-Cas Systems NK Cell Lectin-Like Receptor Subfamily C / genetics Killer Cells, Natural / immunology Receptors, Chimeric Antigen / immunology Gene Editing / methods Leukemia, Myeloid, Acute / immunology Cell Line, Tumor Animals Sialic Acid Binding Ig-like Lectin 3 / genetics Mice Immunotherapy, Adoptive / methods

Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
30 Sep 2024
Historique:
received: 17 01 2023
accepted: 30 08 2024
medline: 1 10 2024
pubmed: 1 10 2024
entrez: 30 9 2024
Statut: epublish

Résumé

Chimeric antigen receptor (CAR)-modified natural killer (NK) cells show antileukemic activity against acute myeloid leukemia (AML) in vivo. However, NK cell-mediated tumor killing is often impaired by the interaction between human leukocyte antigen (HLA)-E and the inhibitory receptor, NKG2A. Here, we describe a strategy that overcomes CAR-NK cell inhibition mediated by the HLA-E-NKG2A immune checkpoint. We generate CD33-specific, AML-targeted CAR-NK cells (CAR33) combined with CRISPR/Cas9-based gene disruption of the NKG2A-encoding KLRC1 gene. Using single-cell multi-omics analyses, we identified transcriptional features of activation and maturation in CAR33-KLRC1

Identifiants

DOI: 10.1038/s41467-024-52388-1 PMID: 39349459
pubmed: 39349459
doi: 10.1038/s41467-024-52388-1
pii: 10.1038/s41467-024-52388-1
doi:

Substances chimiques

NK Cell Lectin-Like Receptor Subfamily C 0
Receptors, Chimeric Antigen 0
KLRC1 protein, human 0
Sialic Acid Binding Ig-like Lectin 3 0
CD33 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

8439

Informations de copyright

© 2024. The Author(s).

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Auteurs

Tobias Bexte (T)

Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.
Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.
Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
German Red Cross Blood Service Baden-Württemberg - Hessen, Institute for Transfusion Medicine and Immunohematology, Frankfurt am Main, Germany.
ORCID: 0009-0009-2392-6416

Nawid Albinger (N)

Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.
Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.
Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.

Ahmad Al Ajami (A)

Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
University Cancer Center (UCT), Frankfurt am Main, Germany.
Goethe University Frankfurt, University Hospital, Neurological Institute / Edinger Institute, Frankfurt am Main, Germany.

Philipp Wendel (P)

Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.
Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.
Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
Institute for Organic Chemistry and Biochemistry, Technical University of Darmstadt, Darmstadt, Germany.
German Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany.
German Cancer Research Center (DKFZ), Heidelberg, Germany.
ORCID: 0000-0001-5844-1587

Leon Buchinger (L)

Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany.
Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.
Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.

Alec Gessner (A)

Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
Goethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.

Jamal Alzubi (J)

Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.
Center for Chronic Immunodeficiency, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
ORCID: 0000-0003-4284-2006

Vinzenz Särchen (V)

Goethe University Frankfurt, Institute for Experimental Pediatric Hematology and Oncology, Frankfurt am Main, Germany.
ORCID: 0000-0001-9565-2850

Meike Vogler (M)

Goethe University Frankfurt, Institute for Experimental Pediatric Hematology and Oncology, Frankfurt am Main, Germany.
ORCID: 0000-0003-2650-586X

Hadeer Mohamed Rasheed (HM)

Charité, University Berlin and Humboldt-University Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany.
Clinical Pathology Department, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
ORCID: 0000-0003-1010-296X

Beate Anahita Jung (BA)

Charité, University Berlin and Humboldt-University Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany.

Sebastian Wolf (S)

Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
German Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany.
Goethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.

Raj Bhayadia (R)

Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.
Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
ORCID: 0000-0003-0865-9582

Thomas Oellerich (T)

Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
German Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany.
Goethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.

Jan-Henning Klusmann (JH)

Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany.
Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
ORCID: 0000-0002-1070-0727

Olaf Penack (O)

Charité, University Berlin and Humboldt-University Berlin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany.
German Cancer Consortium (DKTK) partner site Berlin, Berlin, Germany.
ORCID: 0000-0003-4876-802X

Nina Möker (N)

Miltenyi Biotec B.V. & Co. KG, Bergisch Gladbach, Germany.

Toni Cathomen (T)

Institute for Transfusion Medicine and Gene Therapy, Medical Center - University of Freiburg, Freiburg, Germany.
Center for Chronic Immunodeficiency, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
German Cancer Consortium (DKTK) partner site Freiburg, Freiburg, Germany.
ORCID: 0000-0002-7757-4630

Michael A Rieger (MA)

Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
Goethe University Frankfurt, University Hospital, Department of Medicine II - Hematology and Oncology, Frankfurt am Main, Germany.
Cardio-Pulmonary-Institute, Frankfurt am Main, Germany.
ORCID: 0000-0002-4158-5872

Katharina Imkeller (K)

Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany.
University Cancer Center (UCT), Frankfurt am Main, Germany.
Goethe University Frankfurt, University Hospital, Neurological Institute / Edinger Institute, Frankfurt am Main, Germany.

Evelyn Ullrich (E)

Goethe University Frankfurt, Department of Pediatrics, Experimental Immunology and Cell Therapy, Frankfurt am Main, Germany. evelyn@ullrichlab.de.
Goethe University Frankfurt, Department of Pediatrics, Frankfurt am Main, Germany. evelyn@ullrichlab.de.
Goethe University Frankfurt, Frankfurt Cancer Institute, Frankfurt am Main, Germany. evelyn@ullrichlab.de.
German Cancer Consortium (DKTK) partner site Frankfurt/Mainz, Frankfurt am Main, Germany. evelyn@ullrichlab.de.
ORCID: 0000-0001-8530-1192

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › CRISPR/Cas9 editing of NKG2A improves the...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Extinction de l'expression des gènes › Systèmes CRISPR-Cas › CRISPR/Cas9 editing of NKG2A improves the...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs immunologiques › Récepteurs de cellules tueuses naturelles › Récepteurs de cellules NK de type lectine › Sous-famille C des récepteurs de cellules NK de type lectine › CRISPR/Cas9 editing of NKG2A improves the...
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