A modular and controllable T cell therapy platform for acute myeloid leukemia

  1. Benmebarek, Mohamed-Reda
  2. Cadilha, Bruno L.
  3. Herrmann, Monika
  4. Lesch, Stefanie
  5. Schmitt, Saskia
  6. Stoiber, Stefan
  7. Darwich, Abbass
  8. Augsberger, Christian
  9. Brauchle, Bettina
  10. Rohrbacher, Lisa
  11. Oner, Arman
  12. Seifert, Matthias
  13. Schwerdtfeger, Melanie
  14. Gottschlich, Adrian
  15. Rataj, Felicitas
  16. Fenn, Nadja C.
  17. Klein, Christian ORCID logo
  18. Subklewe, Marion
  19. Endres, Stefan
  20. Hopfner, Karl-Peter ORCID logo
  21. Kobold, Sebastian ORCID logo

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1000 Titel
  • A modular and controllable T cell therapy platform for acute myeloid leukemia
1000 Autor/in
  1. Benmebarek, Mohamed-Reda |
  2. Cadilha, Bruno L. |
  3. Herrmann, Monika |
  4. Lesch, Stefanie |
  5. Schmitt, Saskia |
  6. Stoiber, Stefan |
  7. Darwich, Abbass |
  8. Augsberger, Christian |
  9. Brauchle, Bettina |
  10. Rohrbacher, Lisa |
  11. Oner, Arman |
  12. Seifert, Matthias |
  13. Schwerdtfeger, Melanie |
  14. Gottschlich, Adrian |
  15. Rataj, Felicitas |
  16. Fenn, Nadja C. |
  17. Klein, Christian |
  18. Subklewe, Marion |
  19. Endres, Stefan |
  20. Hopfner, Karl-Peter |
  21. Kobold, Sebastian |
1000 Erscheinungsjahr 2021
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2021-01-07
1000 Erschienen in
1000 Quellenangabe
  • 35(8):2243-2257
1000 Copyrightjahr
  • 2021
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1038/s41375-020-01109-w |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7789085/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Targeted T cell therapy is highly effective in disease settings where tumor antigens are uniformly expressed on malignant cells and where off-tumor on-target-associated toxicity is manageable. Although acute myeloid leukemia (AML) has in principle been shown to be a T cell-sensitive disease by the graft-versus-leukemia activity of allogeneic stem cell transplantation, T cell therapy has so far failed in this setting. This is largely due to the lack of target structures both sufficiently selective and uniformly expressed on AML, causing unacceptable myeloid cell toxicity. To address this, we developed a modular and controllable MHC-unrestricted adoptive T cell therapy platform tailored to AML. This platform combines synthetic agonistic receptor (SAR) -transduced T cells with AML-targeting tandem single chain variable fragment (scFv) constructs. Construct exchange allows SAR T cells to be redirected toward alternative targets, a process enabled by the short half-life and controllability of these antibody fragments. Combining SAR-transduced T cells with the scFv constructs resulted in selective killing of CD33
1000 Sacherschließung
lokal Leukemia, Experimental/pathology [MeSH]
lokal Female [MeSH]
lokal Acute myeloid leukaemia
lokal T-Lymphocytes/immunology [MeSH]
lokal Humans [MeSH]
lokal Leukemia, Myeloid, Acute/immunology [MeSH]
lokal Leukemia, Experimental/immunology [MeSH]
lokal Mice, Inbred NOD [MeSH]
lokal Receptors, Antigen, T-Cell/immunology [MeSH]
lokal Animals [MeSH]
lokal Mice, SCID [MeSH]
lokal Tumor Cells, Cultured [MeSH]
lokal Mice [MeSH]
lokal Article
lokal Leukemia, Experimental/therapy [MeSH]
lokal Xenograft Model Antitumor Assays [MeSH]
lokal T-Lymphocytes/transplantation [MeSH]
lokal Cancer immunotherapy
lokal Targeted therapies
lokal Leukemia, Myeloid, Acute/therapy [MeSH]
lokal Immunotherapy, Adoptive/methods [MeSH]
lokal Leukemia, Myeloid, Acute/pathology [MeSH]
1000 Liste der Beteiligten
  1. https://frl.publisso.de/adhoc/uri/QmVubWViYXJlaywgTW9oYW1lZC1SZWRh|https://frl.publisso.de/adhoc/uri/Q2FkaWxoYSwgQnJ1bm8gTC4=|https://frl.publisso.de/adhoc/uri/SGVycm1hbm4sIE1vbmlrYQ==|https://frl.publisso.de/adhoc/uri/TGVzY2gsIFN0ZWZhbmll|https://frl.publisso.de/adhoc/uri/U2NobWl0dCwgU2Fza2lh|https://frl.publisso.de/adhoc/uri/U3RvaWJlciwgU3RlZmFu|https://frl.publisso.de/adhoc/uri/RGFyd2ljaCwgQWJiYXNz|https://frl.publisso.de/adhoc/uri/QXVnc2JlcmdlciwgQ2hyaXN0aWFu|https://frl.publisso.de/adhoc/uri/QnJhdWNobGUsIEJldHRpbmE=|https://frl.publisso.de/adhoc/uri/Um9ocmJhY2hlciwgTGlzYQ==|https://frl.publisso.de/adhoc/uri/T25lciwgQXJtYW4=|https://frl.publisso.de/adhoc/uri/U2VpZmVydCwgTWF0dGhpYXM=|https://frl.publisso.de/adhoc/uri/U2Nod2VyZHRmZWdlciwgTWVsYW5pZQ==|https://frl.publisso.de/adhoc/uri/R290dHNjaGxpY2gsIEFkcmlhbg==|https://frl.publisso.de/adhoc/uri/UmF0YWosIEZlbGljaXRhcw==|https://frl.publisso.de/adhoc/uri/RmVubiwgTmFkamEgQy4=|https://orcid.org/0000-0001-7594-7280|https://frl.publisso.de/adhoc/uri/U3Via2xld2UsIE1hcmlvbg==|https://frl.publisso.de/adhoc/uri/RW5kcmVzLCBTdGVmYW4=|https://orcid.org/0000-0002-4528-8357|https://orcid.org/0000-0002-5612-4673
1000 Hinweis
  • DeepGreen-ID: 674d9350061146f7a457b5a601f4586b ; metadata provieded by: DeepGreen (https://www.oa-deepgreen.de/api/v1/), LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
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1000 @id frl:6443854.rdf
1000 Erstellt am 2023-04-27T11:05:28.727+0200
1000 Erstellt von 322
1000 beschreibt frl:6443854
1000 Zuletzt bearbeitet 2023-10-20T11:35:00.271+0200
1000 Objekt bearb. Fri Oct 20 11:35:00 CEST 2023
1000 Vgl. frl:6443854
1000 Oai Id
  1. oai:frl.publisso.de:frl:6443854 |
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