Combined Natural Killer T Cell Immunotherapy with Recombinant Vesicular Stomatitis Oncolytic Virus in Ovarian Cancer

Abstract

High relapse rates and limited secondary treatment options make ovarian cancers the leading cause of gynecologic cancer-related deaths in women worldwide. Therefore, development of novel therapeutics with long-lasting outcomes are needed. Natural Killer T (NKT) cells are a rare population of lipid-reactive T-cells, and their infiltration is implicated to improve survival outcomes in several human cancers. Here, we sought to enhance therapeutic benefits of NKT cell activation in the ID8 model of ovarian cancer by incorporating it with recombinant vesicular stomatitis virus (VSV-ΔM51) constructs expressing p14 FAST protein or IL-15. A VSV-ΔM51 construct expressing IL-12 was also engineered to enhance local NKT cell activation. NKT cell therapy significantly prolonged survival and increased tumor immune infiltration whereas the combination therapy with VSV-GFP further enhanced survival. Mice that survived the initial tumor challenge exhibited increased cytotoxicity, and proinflammatory IFNγ production and remained tumor-free following tumor re-challenge, demonstrating formation of immune memory.