William Jia
University of British Columbia, ViroGin Biotech Ltd, Canada
Title: A novel oncolytic HSV-1 vector for cancer immunotherapy
Biography
Biography: William Jia
Abstract
Oncolytic virotherapy has attracted increasing attention as one modality of cancer immunotherapy, especially after FDA approval of T-VEC, the first oncolytic virus (OV) drug in North America. It is now widely accepted that OV induced tumor regression is multi-mechanistic and host immune reaction plays a pivotal role. In the present study, we reported a novel oncolytic HSV-1 virus VG161 that carries three immune stimulating factors: IL12, IL15 with its receptor alpha unit and a PDL-1 blocking peptide. We have shown that this virus expresses the three major factors in infected cancer cells and shown enhanced immune cell cytotoxicity in vitro when co-cultured with PBMC. We also showed that VG161 caused stable and complete tumor regression in both syngeneic mouse tumor and human tumor in nude mouse models. The same tumor failed to grow in previously treated animals. Transcriptional profiling of the tumors treated with VG161 demonstrated a dramatically changed immune microenvironment in the tumor compared to infection with a similar virus VG160 that does not carry the anti-tumor immune stimulating factors. The above results suggest that co-expressing multiple factors by an OV can have enhanced and durable anti-tumor efficacy.