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Review
. 2021 Jul 26;13(8):1450.
doi: 10.3390/v13081450.

Strategies to Optimise Oncolytic Viral Therapies: The Role of Natural Killer Cells

Elaine Y L Leung  1 , Iain A McNeish  2
Affiliations
Review

Strategies to Optimise Oncolytic Viral Therapies: The Role of Natural Killer Cells

Elaine Y L Leung et al. Viruses. .

Abstract

Oncolytic viruses (OVs) are an emerging class of anti-cancer agents that replicate selectively within malignant cells and generate potent immune responses. Their potential efficacy has been shown in clinical trials, with talimogene laherparepvec (T-VEC or IMLYGIC®) now approved both in the United States and Europe. In healthy individuals, NK cells provide effective surveillance against cancer and viral infections. In oncolytic viral therapy, NK cells may render OV ineffective by rapid elimination of the propagating virus but could also improve therapeutic efficacy by preferential killing of OV-infected malignant cells. Existing evidence suggests that the overall effect of NK cells against OV is context dependent. In the past decade, the understanding of cancer and OV biology has improved significantly, which helped refine this class of treatments in early-phase clinical trials. In this review, we summarised different strategies that have been evaluated to modulate NK activities for improving OV therapeutic benefits. Further development of OVs will require a systematic approach to overcome the challenges of the production and delivery of complex gene and cell-based therapies in clinical settings.

Keywords: NK cells; gene therapy; immunotherapy; neoplasms; oncolytic virus.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
NK cell development with summaries of the transcription factors required at each stage of differentiation [28]. NK cells originate from common lymphoid progenitors (CLPs), which differentiate into CILPs (common innate lymphoid progenitors). CILPs then differentiate into NK cell precursors (NKP) or common helper innate lymphoid progenitors (CHILPs). The former give rise to NK cells, and the latter develops into other ILCs. NFIL3 = nuclear factor IL-3 induced; ID2 = inhibitor of DNA binding 2; TOX = thymocyte selection-associated high mobility group box protein; TCF-1 = T cell factor 1; ETS1 = avian erythroblastosis virus E26 homolog-1; GATA3 = GATA binding protein 3; T-bet = T-box transcription factor; Eomes = Eomesodermin.
Figure 2
Figure 2
Potential strategies to augment OV activities via NK cells.
Figure 3
Figure 3
The number of oncolytic virus clinical trials commenced each year since 2010 and registered at ClinicalTrials.gov.
See this image and copyright information in PMC

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