Combination therapy with oncolytic viruses and immune checkpoint inhibitors

ABSTRACT

Introduction: Immune checkpoint inhibitors (ICI) have dramatically improved the outcome for cancer patients across multiple tumor types. However the response rates to ICI monotherapy remain relatively low, in part due to some tumors cultivating an inherently ‘cold’ immune microenvironment. Oncolytic viruses (OV) have the capability to promote a ‘hotter’ immune microenvironment which can improve the efficacy of ICI.

Areas covered: In this article we conducted a literature search through Pubmed/Medline to identify relevant articles in both the pre-clinical and clinical settings for combining OVs with ICIs and discuss the impact of this approach on treatment as well as changes within the tumor microenvironment. We also explore the future directions of this novel combination strategy.

Expert opinion: The imminent results of the Phase 3 study combining pembrolizumab with or without T-Vec injection are eagerly awaited. OV/ICI combinations remain one of the most promising avenues to explore in the success of cancer immunotherapy.

KEYWORDS:

• Cancer
• combination treatment
• immune checkpoint inhibitors
• immunotherapy
• oncolytic viruses

Article Highlights

• Oncolytic viruses (OV) not only selectively infect, replicate inside and kill tumor cells directly, they also have the capability to promote a ‘hotter’ immune microenvironment which can improve the efficacy of ICI.

• T-Vec is the first oncolytic virus to receive FDA and EMA approved in patients with metastatic melanoma.

• Preclinical and clinical studies across many tumor types have shown that OVs promote CD4+, CD8+ T cell tumor infiltration and increase tumoral expression of PD-L1.

• OVs can also be modified to include specific therapeutic transgenes that can enhance the effect of OV/ICI combinations.

• Multiple clinical trials of ICI/OV combinations are ongoing and some have already reported encouraging therapeutic effects.

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Declaration of interest

M Chiu is supported by a grant from Cancer Research UK (CRUK). E Armstrong is supported by a grant from The Wellcome Trust. K Harrington has received research funding from AstraZeneca, Boehringer-Ingelheim, MSD, Replimune and honoraria/advisory board membership (paid to institution) from Amgen, AstraZeneca, BMS, Boehringer-Ingelheim, Merck-Serono, MSD, Mersana Therapeutics, Oncolys, Pfizer, Replimune, Vyriad. A Melcher has received research funding from Oncolytics Biotech Inc, AstraZeneca and honoraria from Amgen, BMS, Merck Serono, Turnstone Biologics Inc. 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 paper was not funded.