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IL-15 superagonist ...
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Van der Meer, J. M. R.
(author)
IL-15 superagonist N-803 improves IFNγ production and killing of leukemia and ovarian cancer cells by CD34+ progenitor-derived NK cells
- Article/chapterEnglish2020
Publisher, publication year, extent ...
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2020-11-03
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Springer Science and Business Media Deutschland GmbH,2020
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:kth-290628
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-290628URI
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https://doi.org/10.1007/s00262-020-02749-8DOI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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Correction in: Cancer Immunology, Immunotherapy volume 70, page3367 (2021). DOI: 10.1007/s00262-021-03049-5, WOS: 000696148000001, Scopus: 2-s2.0-85114867277, QC 20220502
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Allogeneic natural killer (NK) cell transfer is a potential immunotherapy to eliminate and control cancer. A promising source are CD34 + hematopoietic progenitor cells (HPCs), since large numbers of cytotoxic NK cells can be generated. Effective boosting of NK cell function can be achieved by interleukin (IL)-15. However, its in vivo half-life is short and potent trans-presentation by IL-15 receptor α (IL-15Rα) is absent. Therefore, ImmunityBio developed IL-15 superagonist N-803, which combines IL-15 with an activating mutation, an IL-15Rα sushi domain for trans-presentation, and IgG1-Fc for increased half-life. Here, we investigated whether and how N-803 improves HPC-NK cell functionality in leukemia and ovarian cancer (OC) models in vitro and in vivo in OC-bearing immunodeficient mice. We used flow cytometry-based assays, enzyme-linked immunosorbent assay, microscopy-based serial killing assays, and bioluminescence imaging, for in vitro and in vivo experiments. N-803 increased HPC-NK cell proliferation and interferon (IFN)γ production. On leukemia cells, co-culture with HPC-NK cells and N-803 increased ICAM-1 expression. Furthermore, N-803 improved HPC-NK cell-mediated (serial) leukemia killing. Treating OC spheroids with HPC-NK cells and N-803 increased IFNγ-induced CXCL10 secretion, and target killing after prolonged exposure. In immunodeficient mice bearing human OC, N-803 supported HPC-NK cell persistence in combination with total human immunoglobulins to prevent Fc-mediated HPC-NK cell depletion. Moreover, this combination treatment decreased tumor growth. In conclusion, N-803 is a promising IL-15-based compound that boosts HPC-NK cell expansion and functionality in vitro and in vivo. Adding N-803 to HPC-NK cell therapy could improve cancer immunotherapy.
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Maas, R. J. A.
(author)
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Guldevall, KarolinKTH,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1gulq56
(author)
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Klarenaar, K.
(author)
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de Jonge, P. K. J. D.
(author)
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Evert, J. S. H. -V
(author)
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van der Waart, A. B.
(author)
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Cany, J.
(author)
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Safrit, J. T.
(author)
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Lee, J. H.
(author)
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Wagena, E.
(author)
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Friedl, P.
(author)
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Önfelt, B.
(author)
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Massuger, L. F.
(author)
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Schaap, N. P. M.
(author)
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Jansen, J. H.
(author)
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Hobo, W.
(author)
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Dolstra, H.
(author)
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KTHScience for Life Laboratory, SciLifeLab
(creator_code:org_t)
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In:Cancer Immunology and Immunotherapy: Springer Science and Business Media Deutschland GmbH0340-70041432-0851
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Van der Meer, J. ...
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Maas, R. J. A.
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Guldevall, Karol ...
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Klarenaar, K.
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de Jonge, P. K. ...
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Evert, J. S. H. ...
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van der Waart, A ...
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Cany, J.
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Safrit, J. T.
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Lee, J. H.
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Wagena, E.
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Friedl, P.
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Önfelt, B.
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Massuger, L. F.
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Schaap, N. P. M.
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Jansen, J. H.
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Hobo, W.
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Dolstra, H.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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Cancer Immunolog ...
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Royal Institute of Technology