RE:RE:RE:RE:RE:ONCY's pelareorep activates interferon (IFN) signalling
ONCY's pelareorep (reovirus) is capable of remodeling an immunosuppressive / hypoxic tumor microenvironment (TME) through the downregulation of HIF-1α target genes in tumor cells. The result is that ONCY's pelareorep is able to "prime" the innate immune system in advance of the addition of PD-(L)1 immune checkpoint inhibitors to produce a synergistic outcome seen by adding the 2 agents together rather than that seen in using either agent alone. as a montherapy.
ONCY's pelareorep reduces HIF-1α expression in hypoxic tumor fractions, contributing to the overall oncolytic effect by reducing transcription of HIF1α-responsive genes including VEGF and those responsible for maintaining cancer stem cell phenotypes.
Many groups have attempted to target hypoxic fractions using hypoxia-specific promoters, however these are often less powerful drivers of gene expression compared to ONCY's oncolytic virus pelareorep.
HIF-1α is a strong inducer of CD39, CD38 and the A2Rs that are key mediators of extracellular adenosine signaling in the TME, so therefore ONCY's pelareorep-mediated elimination of hypoxic fractions can also effect changes in the adenosinergic environment.
Adenosine signaling in the TME activates intracellular cyclic adenosine monophosphate and is associated with profound immune suppression. (Ohta A, Gorelik E, Prasad SJ, et al.)
Along with the ability to be combined with PD-(L)1 immune checkpoint inhibitors, ONCY's pelareorep can also be used in combination with small molecule inhibitors or those mAbs targeting these adenosine signaling receptors, many of which are being investigated clinically (Vigano S, Alatzoglou D, Irving M, et al.) to reduce the accumulation and activity of extracellular adenosine.