Oncolytic activity of the rhabdovirus VSV‐GP against prostate cancer

Abstract

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.

Self-amplifying RNA virus vectors: clinical applications in cancer drug delivery

“…The combined DNA vaccine provided therapeutic activity by superior inhibition of tumor growth and prolonged survival in a B16 melanoma mouse model compared to immunization with individual SFV DNA vectors. Moreover, therapeutic efficacy was observed after intratumoral administration of an oncolytic pseudotyped vesicular stomatitis virus (VSV-GP), which generated long-term remission in murine prostate cancer models, also in subcutaneous tumors and bone metastases after intravenous administration [11]. Additional studies have confirmed therapeutic tumor regression in lung (MV particles and SFV VLPs), ovarian (oncolytic VSV particles and Sindbis virus VLPs), and pancreatic cancers [1].…”

Self-Amplifying RNA Viruses as RNA Vaccines

“…The survival rate was 90% at 12 months in immunized mice compared to control mice, who had either succumbed to prostate cancer or presented a heavy tumor load. In another study, the prostate-specific antigen (PSA) was expressed from a VEE vector showing efficient infection of mouse DCs in vitro and eliciting a robust PSA-specific response in vivo [ 127 ]. Furthermore, immunization with VEE-PSA strongly stimulated production of IgG2a/b anti-PSA antibodies and tumor growth was significantly delayed.…”

“…The study showed that immunization can overcome immune tolerance to PSA and can mediate rapid clearance of PSA-expressing tumor cells. Related to VSV vectors, the VSV-GP-LCMV expressing luciferase showed great efficacy of infection of prostate cancer cell lines and long-term remission in Du145 and 22Rv1 prostate cancer models after intratumoral injections [ 127 ]. Moreover, remission was also observed in syngeneic TRAMP-C subcutaneous tumors and after intravenous vector administration in PC-3M-Luc bone metastases.…”

RNA Viruses as Tools in Gene Therapy and Vaccine Development

“…The response in both subcutaneous and orthotopic xenograft models could be enhanced by combination therapy with ruxilitinib. The pseudotyped VSV-GP also provided long-term remission in prostate cancer mouse models after intratumoral injections [101]. Furthermore, intravenous administration of subcutaneous tumors and bone metastases resulted in remission.…”