Therapeutic Effect on Bladder Cancer with aConditionally Replicating Oncolytic Virus Derived from Type II Herpes Simplex Virus.

Abstract

Purpose:Despite recent improvements, resistance to traditional immunotherapy or chemotherapy is still common in patients with bladder cancer. We constructed an oncolytic virus from herpes simplex virus type II (HSV-2), which selectively targets tumor cells with an activated Ras signaling pathway. We evaluated the antitumor effect of this oncolytic HSV-2 (FusOn-H2) against bladder cancer, and compared with that of a first generation oncolytic virus derived from HSV-1 (Baco-1).Materials and methods: We established bladder tumor at the orthotopic site in C3H/He mice using the MBT-2 cells. Baco-1 or FusOn-H2 was instilled into the bladder through the urethra respectively. Tumor volume and weight were recorded by the end of the experiment. Animal spleens were also collected to determine if any anti-tumor immunity was elicited during virotherapy in this syngeneic bladder cancer model.Results: Two instillations of the oncolytic HSVs into bladder of tumor-bearing mice almost completely eradicated the tumor in majority of tumor bearing mice. The results of tumor-specific cytotoxic T lymphocyte activity assay showed that tumor destruction by oncolytic viruses in vivo, especially by the FusOn-H2, induced potent anti-tumor immune responses.Conclusion: Oncolytic virus derived from HSV-2 has potent anti-tumor activity against bladder cancer. Oncolytic effect of this virus in vivo induces tumor specific cellular immunity that further enhances the overall anti-tumor activity. Translating this novel virotherapy into the clinic could present an alternative intravesical therapy strategy for patients with bladder cancer.