Capitalizing on Cancer Specific Replication: Oncolytic Viruses as a Versatile Platform for the Enhancement of Cancer Immunotherapy Strategies

Abstract

The past decade has seen considerable excitement in the use of biological therapies in treating neoplastic disease. In particular, cancer immunotherapy and oncolytic virotherapy have emerged as two frontrunners in this regard with the first FDA approvals for agents in both categories being obtained in the last 5 years. It is becoming increasingly apparent that these two approaches are not mutually exclusive and that much of the therapeutic benefit obtained from the use of oncolytic viruses (OVs) is in fact the result of their immunotherapeutic function. Indeed, OVs have been shown to recruit and activate an antitumor immune response and much of the current work in this field centers around increasing this activity through strategies such as engineering genes for immunomodulators into OV backbones. Because of their broad immunostimulatory functions, OVs can also be rationally combined with a variety of other immunotherapeutic approaches including cancer vaccination strategies, adoptive cell transfer and checkpoint blockade. Therefore, while they are important therapeutics in their own right, the true power of OVs may lie in their ability to enhance the effectiveness of a wide range of immunotherapies.

Overexpression of Smac by an Armed Vesicular Stomatitis Virus Overcomes Tumor Resistance

“…Cancer cells are usually developed under stress conditions, which may prepare these cells to resist stress to limit virus infection. Several strategies have been tested to exploit the synergetic effects of checkpoint inhibitors and OVs 34, 35, 36, 37. Other anticancer agents have also been used to sensitize cancer cells to OVs, including Smac mimetics 11, 38, 39.…”

Oncolytic Immunotherapy: Conceptual Evolution, Current Strategies, and Future Perspectives

“…Thus, there exists obvious potential for synergy between therapeutic regimens using OVs and immune checkpoint blockade. Mechanistically, OVs offer the possibility of priming, boosting, and recruiting effector T cells into the TME, where immune checkpoint blockade may serve to enhance/sustain the potency of antitumor TIL via the removal of inhibitory signals ( 94 , 107 ).…”

Editorial of the Special Issue: Oncolytic Viruses as a Novel Form of Immunotherapy for Cancer

“…Wan and associates discuss how to utilize OVs as platforms to enhance immunotherapy strategies [ 7 ]. They provide an excellent summary of experimental studies that have led to the realization that the immune response is paramount in OV-mediated therapy.…”