Recombinant Poxvirus and the Tumor Microenvironment: Oncolysis, Immune Regulation and Immunization

Abstract

Oncolytic viruses (OVs) are being extensively studied for their potential roles in the development of cancer therapy regimens. In addition to their direct lytic effects, OVs can initiate and drive systemic antitumor immunity indirectly via release of tumor antigen, as well as by encoding and delivering immunostimulatory molecules. This combination makes them an effective platform for the development of immunotherapeutic strategies beyond their primary lytic function. Engineering the viruses to also express tumor-associated antigens (TAAs) allows them to simultaneously serve as therapeutic vaccines, targeting and amplifying an immune response to TAAs. Our group and others have shown that vaccinating intratumorally with a poxvirus that encodes TAAs, in addition to immune stimulatory molecules, can modulate the tumor microenvironment, overcome immune inhibitory pathways, and drive both local and systemic tumor specific immune responses.

Improving antitumor efficacy via combinatorial regimens of oncolytic virotherapy

“…Intratumoral co-treatment with separate vaccinia virus expressing GM-CSF and HER2 decreased levels of MDSCs and enhanced systemic antitumor activity in MDSC-rich tumors compared to treatment with either of the individual viruses alone [ 134 ]. It is also possible to incorporate a cytokine and TAA into the same viral vector [ 135 ]. Another notable approach involving TAA-encoding OVs is the heterologous prime-boost immune strategy that can focus immune responses toward the tumor antigens and away from viral antigens.…”

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

“…Lattime and Sharp discuss the use of recombinant poxviruses to modulate the TME for cancer immunotherapy [ 11 ]. Their key point is that intratumoral vaccination of a poxvirus encoding TAA and immune stimulatory molecules can modulate the TME, inhibiting the immune inhibitory pathways and drive both local and systemic anti-tumor immunity.…”

Poxviruses Utilize Multiple Strategies to Inhibit Apoptosis

“…Further, because the human population is no longer vaccinated, the intentional or unintentional release of Variola Virus (VARV), the causative agent of smallpox, remains a concern. Poxviruses also represent attractive vectors with many medically relevantuses ranging from vaccines to use as oncolytic viruses [ 78 , 79 , 80 ]. Therefore, understanding how these viruses modulate host immune responses, including cellular apoptotic pathways, remains a research priority.…”