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.
Highlights
T-cell immunoglobulin and ITIM domain protein (TIGIT) blockade was previously shown to prevent Natural Killer (NK) cell exhaustion and promote NK-dependent anti-tumoural responses in murine models [74], whilst we showed that TIGIT blockade could augment the NK cytotoxicity of oncolytic adenovirus-infected human ovarian cancer cells [67]
NK cells are the prime immune cell population to control viral infections in humans, their ability to eliminate viral-infected cellscells rapidly could leadlead to opposing impacts on the but their ability to eliminate viral-infected rapidly could to opposing impacts on therapeutic outcomes of oncolytic viral therapies
Existing evidence suggests the overeffect of NK cell response on the efficacy of Oncolytic viruses (OVs) is context dependent
Summary
Oncolytic viruses (OVs) are an emerging class of anti-cancer agents, with proven efficacy in randomised clinical trials and potential to produce durable treatment response [1,2,3]. Measles viral entry receptors (e.g., CD46) are highly expressed by many tumour cells [8]. Talimogene laherparepvec (T-VEC or IMLYGIC® ) [2,14] is an oncolytic herpes simplex virus (HSV) engineered to express human granulocyte macrophage colony-stimulating factor (hGM-CSF) to augment anti-tumoural T-cell responses [15,16]. The regulatory approval of T-VEC and the fact that T-VEC expresses hGM-CSF, an important haematopoietic growth factor and immune modulator, have incentivised research and further clinical trials on improving the efficacy of OV by enhancing antitumoural immune responses. We provide concise summaries and key references on NK cell development and the determinants of NK responses for those less familiar with this immune cell population
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
