A vector-encoded bispecific killer engager to harness virus-activated NK cells as anti-tumor effectors
Treatment with oncolytic measles vaccines (MV) elicits activation of immune cells, including natural killer (NK) cells. However, we found that MV-activated NK cells show only modest direct cytotoxic activity against tumor cells. To specifically direct NK cells towards tumor cells, we developed oncol...
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| Hauptverfasser: | , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
10 February 2023
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| In: |
Cell death & disease
Year: 2023, Jahrgang: 14, Heft: 2, Pages: 1-15 |
| ISSN: | 2041-4889 |
| DOI: | 10.1038/s41419-023-05624-3 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41419-023-05624-3 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41419-023-05624-3 
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| Verfasserangaben: | Alessia Floerchinger, Jessica E. Klein, Maximiliane S.C. Finkbeiner, Theresa E. Schäfer, Gwendolin Fuchs, Johannes Doerner, Hubert Zirngibl, Maximilian Ackermann, Hans M. Kvasnicka, Kerry A. Chester, Dirk Jäger, Claudia R. Ball, Guy Ungerechts and Christine E. Engeland |
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| 520 | |a Treatment with oncolytic measles vaccines (MV) elicits activation of immune cells, including natural killer (NK) cells. However, we found that MV-activated NK cells show only modest direct cytotoxic activity against tumor cells. To specifically direct NK cells towards tumor cells, we developed oncolytic measles vaccines encoding bispecific killer engagers (MV-BiKE) targeting CD16A on NK cells and carcinoembryonic antigen (CEA) as a model tumor antigen. MV-BiKE are only slightly attenuated compared to parental MV and mediate secretion of functional BiKE from infected tumor cells. We tested MV-BiKE activity in cocultures of colorectal or pancreatic cancer cells with primary human NK cells. MV-BiKE mediate expression of effector cytokines, degranulation and specific anti-tumor cytotoxicity by NK cells. Experiments with patient-derived pancreatic cancer cultures indicate that efficacy of MV-BiKE may vary between individual tumors with differential virus permissiveness. Remarkably, we confirmed MV-BiKE activity in primaryhuman colorectal carcinoma specimens with autochthonous tumor and NK cells.This study provides proof-of-concept for MV-BiKE as a novel immunovirotherapy to harness virus-activated NK cells as anti-tumor effectors. | ||
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