Thunder and lightning: immunotherapy and oncolytic viruses collide

Abstract

For the last several decades, the development of antitumor immune-based strategies and the engineering and testing of oncolytic viruses (OVs) has occurred largely in parallel tracks. Indeed, the immune system is often thought of as an impediment to successful oncolytic virus delivery and efficacy. More recently, however, both preclinical and clinical results have revealed potential synergy between these two promising therapeutic strategies. Here, we summarize some of the evidence that supports combining OVs with immuno-therapeutics and suggest new ways to mount a multipronged biological attack against cancers.

Figure 1

It takes two to tango: striking the balance between antitumor activity, and antivector immunity. (a) Immune barriers to oncolytic virus (OV) delivery/spread. (b) Antitumor immune activity. (c) Blockade/suppression of immune activity. CAR, chimeric antigen receptor; CTL, cytotoxic T lymphocyte; DC, dendritic cell; IDO, indoleamine 2,3-dioxygenase; IFN, interferon; IL, interleukin; MHC, major histocompatibility complex; NK, natural killer cell; TGF-β, transforming growth factor-β TIL, tumor infiltrating lymphocyte; VEGF, vascular endothelial growth factor.

Figure 2

Combining oncolytic virotherapy with tumor-specific T cells. Oncolytic virus (OV)-specific T cells could be expanded ex vivo after the second vaccination. If the individual was already exposed to the OV by vaccination or prior infection, then the T cells could be manufactured earlier. After activation, the T cells could be transduced with a retroviral vector expressing a tumor-specific chimeric antigen receptor (CAR) to redirect their specificity to a tumor antigen. The transduced cytotoxic T lymphocytes (CTLs) could then be infused after virotherapy when the tumor load would be reduced. The OV could then be used as a vaccine to induce T-cell expansion and maintain function.