Oncolytics Biotech Inc ONCY

RE:RE:RE:RE:reo and t cell-based strategies

[Noteable]

One of the directions that is being taken is to combine bi- or tri- specific T-cell engagers (BiTE or TriTE) with OVs to directly stimulate T-cell immunity without antigen presentation by APCs. This notwithstanding , it has been demonstrated that the response to reovirus-based therapy can be an indication that reovirus oncolytic virus-based treatments can reshape the tumor microenvironment (TME). It was later shown that reovirus oncolytic viral-based treatments increase proinflammatory cytokines in the TME, enhance the cytotoxicity of innate immune cells, and augment antigen presentation and adaptive immune responses.

For example, in a study by Muller et al., reovirus treatment increased the number of NK and cytotoxic T cells, which also exhibited a stronger activated phenotype. In addition, reovirus treatment enhanced the memory response of the immune system. Altogether, it has been shown that reovirus significantly alters the immune response towards the tumor.

Studies have demonstrated that reovirus-activated NK cells together with monoclonal antibody treatment synergistically enhance their anti-tumor cytotoxicity in colorectal cancer model (Long S. et al 2021), and that reovirus enhances rituximab-mediated NK cytotoxicity against chronic lymphocytic leukemia (42). Moreover, checkpoint inhibition was shown to improve the ability of NK cells to kill reovirus-infected tumor cells (Rajani K, et al 2016).

It has been postulated the ability of the reovirus to restrain NK cell cytotoxicity may limit the elimination of tumor cells but will enable better spread of the reovirus in the tumor microenvironment, which could improve the oncolytic activity of virus-based treatments. 

Shedding of the NKG2D ligand has been observed in response to hypoxia. High levels of HIF1α have been correlated with decreased expression of MICA/B on pancreatic tumour cells and also with increased internalisation of the activating receptor NKG2D, suggesting a dual role for the hypoxic TME in NK cell dysfunction, which I have posted on in past posts.

ONCY's pelareorep is able to down regulate HIF1α , which reduces the levels of HIF1α and remodels the TME in advance of the addition of immune checkpoint inhibitors.

New results suggest that reovirus-based therapies may be of special interest in tumors with high shedding of NKG2D ligands, namely breast, pancreatic, colorectal, ovarian, and GI cancers.

https://www.frontiersin.org/articles/10.3389/fimmu.2023.1231782/full#B41