Journal Article

DKFZ-2023-00314

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png A vector-encoded bispecific killer engager to harness virus-activated NK cells as anti-tumor effectors.

Floerchinger, A. (First author)DKFZ* ; Klein, J. E.DKFZ* ; Finkbeiner, M. S. C. ; Schäfer, T.DKFZ* ; Fuchs, G.DKFZ* ; Doerner, J. ; Zirngibl, H. ; Ackermann, M. ; Kvasnicka, H. M. ; Chester, K. A. ; Jäger, D. ; Ball, C. R.DKFZ* ; Ungerechts, G.DKFZ* ; Engeland, C. (Last author)DKFZ*

2023
Nature Publishing Group London [u.a.]

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Please use a persistent id in citations: doi:10.1038/s41419-023-05624-3

Abstract: 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.

Note: #EA:F230#LA:F230#

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Contributing Institute(s):

1. KKE Virotherapie (F230)
2. DKTK DD zentral (DD01)

Research Program(s):

1. 316 - Infektionen, Entzündung und Krebs (POF4-316) (POF4-316)

Appears in the scientific report 2023

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