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Oncolytic virotherapy can self-amplify intratumorally, thereby increasing its dose in situ. This innovative approach holds promise for cancers resistant to existing treatments.
Oncolytic viruses (OVs) have been shown to:
For this reason, Oncolytic virus (OV) serve as ideal complements to Immune checkpoint inhibitors (ICIs). Multiple preclinical studies and clinical trials are demonstrating their combined therapeutic efficacy.
Oncolytic viruses were divided with respect to the genome in DNA and RNA viruses
Oncolytic viruses (OVs) are engineered to specifically target and kill cancer cells while simultaneously triggering an immune response at the site of infection
Oncolytic viruses (OV) have a double oncolytic action by both directly destroying the cancer cells and stimulating a tumor specific immune response to return the ability of tumors to escape the control of the immune system
These viruses range from small picornaviruses to large Poxviruses / Poxviridae and are currently being investigated as potential candidates.
Initially, non-engineered wild-type or vaccine-strain viruses were used. However, these did not fully meet the criteria for safety and efficacy. With the advent of reverse genetics systems, the focus has shifted to genetically engineered viruses with an improved therapeutic index ().
Oncolytic viruses have been shown to:
Oncolytic virus vectors being explored include:
Oncolytic vectors can induce anti-tumor immunity and significantly increase immune cell infiltration (including Cytotoxic T cell (CTL)) into the local tumor microenvironment (). This "priming" by the viral infection can change a 'cold' tumor microenvironment into a 'hot' one with the influx of a multitude of immune cells and cytokines ()
This alteration sets the stage for subsequent checkpoint inhibitor delivery, which is most effective in an environment with a large lymphocytic infiltrate (). Multiple ongoing clinical trials are currently combining oncolytic viruses with checkpoint inhibitors, such as:
The initial results are encouraging, with more than 15 ongoing clinical trials employing a combination regimen of these two types of cancer therapeutics
Recent large-scale phase III trials, such as PHOCUS and OPTiM, are establishing the use of oncolytic viruses as another tool in the cancer therapeutics armamentarium
Oncolytic adenovirus shows an antitumoral effect via its intratumoral amplification and strong cytocidal effect in a variety of cancers (). Furthermore, CD274 (Programmed death-ligand 1 (PD-L1)) expression increases on tumor and immune cells following viral infection ().
Oncolytic viruses are naturally occurring or genetically modified viruses that infect, replicate, and kill cancer cells without harming normal cells (). Following viral infection, there are increased levels of local cytokine expression and an influx of immune cells, including natural killer (NK) cells, activated T cells, and antigen-presenting cells (APC) ().