Abstract
Recent cancer immunotherapy breakthroughs have fundamentally changed oncology and revived the fading hope for a cancer cure. The immune checkpoint inhibitors (ICI) became an indispensable tool for the treatment of many malignant tumors. Alongside ICI, the application of oncolytic viruses in clinical trials is demonstrating encouraging outcomes. Dozens of combinations of oncolytic viruses with conventional radiotherapy and chemotherapy are widely used or studied, but it seems quite complicated to highlight the most effective combinations. Our review summarizes the results of clinical trials evaluating oncolytic viruses with or without genetic alterations in combination with immune checkpoint blockade, cytokines, antigens and other oncolytic viruses as well. This review is focused on the efficacy and safety of virotherapy and the most promising combinations based on the published clinical data, rather than presenting all oncolytic virus variations, which are discussed in comprehensive literature reviews. We briefly revise the research landscape of oncolytic viruses and discuss future perspectives in virus immunotherapy, in order to provide an insight for novel strategies of cancer treatment.
Highlights
Immunotherapy is arguably the most rapidly evolving field of cancer treatment
This review is focused on the efficacy and safety of virotherapy and the most promising combinations based on the published clinical data, rather than presenting all oncolytic virus variations, which are discussed in comprehensive literature reviews
We briefly revise the research landscape of oncolytic viruses and discuss future perspectives in virus immunotherapy, in order to provide an insight for novel strategies of cancer treatment
Summary
Immunotherapy is arguably the most rapidly evolving field of cancer treatment. Despite the long history of cancer being treated mainly by the “cut, poison and burn” principle, immunotherapeutics allowed to outsmart the tumor using the intrinsic potential of the immune system. Adenoviruses possess some advantageous characteristics for cancer gene therapy, such as high efficiency of gene transfer in both dividing and non-dividing cells, a low risk of insertion mutagenesis, and replication in an exponential manner (having entered an infected cell, one virus can produce more than 10,000 progeny viruses). They have a wide range of tissue tropism and relatively large DNA loading capacity (up to 8.5 kb DNA in the case of adenovirus that contains a DNA genome of 36 kb) [41]. No difference in terms of overall survival was observed [47]
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