Current strategies in engaging oncolytic viruses with antitumor immunity

Abstract

Oncolytic virotherapy has produced promising yet limited results in preclinical and clinical studies. Besides direct oncolytic activity, a significant therapeutic mechanism of oncolytic virotherapy is the induction of tumor-specific immunity. Consequently, the efficacy of oncolytic viruses can be improved by the insertion of immune stimulator genes and rational combinatorial therapy with other immunotherapies. This article reviews recent efforts on arming oncolytic viruses with a variety of immune stimulator molecules, immune cell engagers, and other immune potentiating molecules. We outline what is known about the mechanisms of action and the corresponding results. The review also discusses recent preclinical and clinical studies of combining oncolytic virotherapy with immune-checkpoint inhibitors and the role of oncolytic virotherapy in changing the tumor microenvironment.

Graphical abstract

Figure 1

Armed OVs and their mechanism of action Mechanism-1: Direct oncolysis by the virus, which also triggers NK and T cell infiltration. Mechanism-2: Specifically designed armed viruses can release NK/T cell engagers to activate these immune cells to kill more tumor cells. Together with Mechanism-1, abundant TAAs (including neoantigens) will be released from the lysed tumor cells. Mechanism-3: The activated NK cells can secrete additional cytokines/chemokines (e.g., XCL1-a C class chemokine also known as lymphotactin) to attract conventional DCs (cDCs) to capture TAAs. Armed viruses can also release other immune stimulators such as GM-CSF and interleukins that can further potentiate TAA presentation. Chemokines released from subsequent virotherapy can attract the migration of TAA-specific T cells back to the tumor site.