NK Cell Effector Functions and Bystander Tumor Cell Killing in Immunovirotherapy

Floerchinger, Alessia; Engeland, Christine E.

doi:10.1007/978-1-0716-2441-8_12

Cited by 1 publication

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“…Target cell killing assays Flow cytometry: Killing of tumor cells by IL-2 pre-stimulated NK cells was assessed using a flow cytometry-based cytotoxicity assay (adapted from [64]). In principle, non-infected target cells were labeled with 5 µM Celltrace CFSE (Thermo Fisher Scientific) according to the manufacturer's instructions and killing was quantified after co-incubation with NK cells and either vBiKEs or MV-BiKE-infected tumor cells as previously described [65].…”

Section: Functional In Vitro Coculture Assaysmentioning

confidence: 99%

A vector-encoded bispecific killer engager to harness virus-activated NK cells as anti-tumor effectors

et al. 2023

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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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Section: Functional In Vitro Coculture Assaysmentioning

confidence: 99%