Oncolytic activity of the rhabdovirus VSV‐GP against prostate cancer

Oncolytic viruses, including the oncolytic rhabdovirus VSV‐GP tested here, selectively infect and kill cancer cells and are a promising new therapeutic modality. Our aim was to study the efficacy of VSV‐GP, a vesicular stomatitis virus carrying the glycoprotein of lymphocytic choriomeningitis virus, against prostate cancer, for which current treatment options still fail to cure metastatic disease. VSV‐GP was found to infect 6 of 7 prostate cancer cell lines with great efficacy. However, susceptibility was reduced in one cell line with low virus receptor expression and in 3 cell lines after interferon alpha treatment. Four cell lines had developed resistance to interferon type I at different levels of the interferon signaling pathway, resulting in a deficient antiviral response. In prostate cancer mouse models, long‐term remission was achieved upon intratumoral and, remarkably, also upon intravenous treatment of subcutaneous tumors and bone metastases. These promising efficacy data demonstrate that treatment of prostate cancer with VSV‐GP is feasible and safe in preclinical models and encourage further preclinical and clinical development of VSV‐GP for systemic treatment of metastatic prostate cancer. What's new? While oncolytic viruses are promising antitumor agents, those currently under development exhibit variability between patients in their effectiveness against tumors. In this study, multiple prostate cancer cell lines were found to differ in their susceptibility to killing by the oncolytic rhabdovirus VSV‐GP. Despite this, VSV‐GP was highly effective in prostate cancer mouse models. When administered intratumorally or intravenously, VSV‐GP produced long‐term remission of subcutaneous tumors and bone metastases. The data suggest that, with further development, VSV‐GP could be a clinically valuable agent for the systemic treatment of metastatic prostate cancer.