Maria Davola, McMaster University

Maria Davola (1), Olga Cormier (1), Madeleine Lepard (1), Susan Collins (1), Amy Gillgrass (2), Karen Mossman (1) – (1) Department of Medicine, Centre for Discovery in Cancer Research, McMaster University, Hamilton ON Canada, and (2) Department of Microbiology and Immunology, Dalhousie University, Halifax NS Canada.

Fighting & Responding

Pancreatic ductal adenocarcinoma (PDAC) is one of the most challenging malignancies to treat today. Bovine herpesvirus type 1 (BHV-1) is a relative of herpes simplex type 1 (HSV-1) that targets a wider range of cancer cells, including the entire ATCC human pancreatic cancer panel. Further, BHV-1 is not neutralized by human serum allowing systemic delivery for the treatment of both primary and metastatic cancers. In syngeneic mouse cancer models BHV-1 activates and recruits CD8 tumor infiltrating lymphocytes (TILs) but, as with many oncolytic viruses (OVs), needs to be combined with other immunotherapies to significantly increase animal survival. To extend BHV-1 pre-clinical studies to PDAC, we used humanized mice that better reproduce the interactions between patient tumor and immune cells. Given the importance of CD8 T cells in BHV-1's mechanism of action, we developed a humanized PDAC model with HLA class I match using transgenic mice expressing HLA-A2.1. While BHV-1 fails to control tumor growth in non-humanized mice bearing PDAC tumors reflecting lack of tumor killing capacity per se, complete tumor regression was observed in 5 out of 7 humanized mice. While non-responders and PBS showed similar levels of tumor infiltrating immune cells, higher levels of TILs, including B cells, CD4 and CD8 T cells, were observed in BHV-1 responders. Overall, our findings show the clinical potential of BHV-1 for the treatment of PDAC. Ongoing studies are focused on better understanding BHV-1's mechanism of action.