TY  - JOUR
AU  - Floerchinger, Alessia
AU  - Klein, Jessica E
AU  - Finkbeiner, Maximiliane S C
AU  - Schäfer, Theresa
AU  - Fuchs, Gwendolin
AU  - Doerner, Johannes
AU  - Zirngibl, Hubert
AU  - Ackermann, Maximilian
AU  - Kvasnicka, Hans M
AU  - Chester, Kerry A
AU  - Jäger, Dirk
AU  - Ball, Claudia R
AU  - Ungerechts, Guy
AU  - Engeland, Christine
TI  - A vector-encoded bispecific killer engager to harness virus-activated NK cells as anti-tumor effectors.
JO  - Cell death & disease
VL  - 14
IS  - 2
SN  - 2041-4889
CY  - London [u.a.]
PB  - Nature Publishing Group
M1  - DKFZ-2023-00314
SP  - 104
PY  - 2023
N1  - #EA:F230#LA:F230#
AB  - 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.
LB  - PUB:(DE-HGF)16
C6  - pmid:36765035
DO  - DOI:10.1038/s41419-023-05624-3
UR  - https://inrepo02.dkfz.de/record/267536
ER  -