Arming oncolytic viruses to leverage antitumor immunity

Over the past decade, the cytolytic capabilities of oncolytic viruses (OVs), exploited to selectively eliminate neoplastic cells, have become secondary to their use to elicit a tumor-directed immune response.

Here, based on an NCBI-PubMed literature survey, we review the efforts undertaken to arm OVs in order to improve therapeutic antitumor responses upon administration of these agents. Specifically, we explore the different options to modulate immune suppression in the tumor microenvironment (TME) and to facilitate the generation of effective antitumor responses that have been investigated in conjunction with OVs in recent years.

Their induction of immunogenic tumor cell death and association with pro-inflammatory signals make OVs attractive immunotherapeutic modalities. The first promising clinical results with immunologically armed OVs warrant their further optimization and development. OVs should be modified to avoid detrimental effects of pre-existent anti-OV immunity as well as for increased tumor targeting and selectivity, so as to ultimately allow for systemic administration while achieving local immune potentiation and tumor elimination in the TME. In particular, a combination of trans-genes encoding bispecific T-cell engagers, immune checkpoint blockers and antigen-presenting cell enhancers will remove suppressive hurdles in the TME and allow for optimal antitumor efficacy of armed OVs.