Combining oncolytic virus with FDA approved pharmacological agents for cancer therapy

ABSTRACT

Introduction

Oncolytic viruses (OVs) have been engineered to selectively replicate in cancer cells. While initially thought to exert its anti-cancer effects through direct cytolysis, it is increasingly appreciated that OVs interact with a multitude of cellular processes during its life cycle; FDA approved pharmacologic agents that modulate these cellular processes have been shown to augment the anti-neoplastic effects of OVs. Moreover, because of the release of tumor antigens as well as the innate immuno-stimulatory nature of viruses, OVs induce potent immune responses that augment the anti-tumor effects of FDA approved immunotherapies. There is mounting interest in OV as a platform for combinational anti-cancer therapy in this context.

Areas covered

We will review pre-clinical and clinical data that demonstrate proof-of-principle and potential efficacy for OV-based combination therapies with FDA approved anti-cancer agents.

Expert opinion

While the cytolytic activity of OV remains a key driver for its anti-neoplastic effects, understanding the virus–host interactions may afford opportunities for potential synergism with FDA approved therapeutics that target these interactions. Most intriguingly, the immune stimulatory effects of OVs renders combination with FDA approved immunotherapies more potent. While there are growing clinical trials employing such combination therapy, meaningful advances in this paradigm will require improved understanding of virus–host interactions.

KEYWORDS:

• Oncolytic virus
• approved agents
• combination therapy

Article highlights

• Oncolytic viruses (OVs) interact with a multitude of cellular pathways during its life cycle, including DNA repair and mitogenesis.

• FDA approved pharmacologic agents targeting the cellular pathways that OV modulate augment or synergize with the anti-cancer effects of OV.

• In addition to directly lysing the cancer cells, OV induces potent immune responses that augment the anti-tumor effects of FDA approved immunotherapies.

• There is escalating clinical interest in OVs as a platform for rational design of multi-regimen, anti-cancer therapy.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This work was supported by the foundation Humor to Fight the Tumor.