Introduction
tumor, melanoma, herpes, flu-like illness, immune-mediated destruction, CM, tumor death
VESICULAR STOMATITIS, VIRUS, TUMOR, MELANOMA, HERPES, LYSIS, SECONDARY, FLU-LIKE ILLNESS, ONCOLYSIS
The treatment landscape for melanoma rapidly evolved after the introduction of immune checkpoint inhibitors (ICIs). Prior to ICI approval, the 5-year survival for melanoma was 18.3% in 2010, which has increased to 31.9% based on 2018 data (The difference in response to ICIs may in part be due to UM having a lower tumor mutational burden (TMB) and PD-L1 expression compared to CM, even when samples are analyzed from the same metastatic site (Oncologic viruses (OV) are a novel approach to immunotherapy in that they can induce tumor death through both direct oncolysis and immune-mediated destruction. Currently, the only FDA-approved OV is talimogene laherparepvec (T-VEC), an intralesional injection of a modified herpes virus that leads to tumor lysis and granulocyte macrophage colony-stimulating factor (GM-CSF) delivery. T-VEC is used in unresectable CM based on improved response rates (RR) compared to GM-CSF alone (Our study investigates the use of a novel OV, a vesicular stomatitis virus (VSV) vector modified to express interferon-beta (IFN-β) and Tyrosinase Related Protein 1 (TYRP1) (VSV-IFNβ-TYRP1). VSV as a vector is appealing since this virus does not naturally infect humans. In rare circumstances when humans are infected, they are asymptomatic or have a mild flu-like illness that resolves spontaneously within a few days and is not contagious to other humans (We report the results of our phase 1 clinical trial investigating VSV-IFNβ-TYRP1 in previously treated patients with MUM, via IT and IV administration. The primary endpoint was safety. Efficacy was a secondary endpoint. Correlative studies focused on understanding viral pharmacokinetics (PK) and the immunological responses induced by VSV-IFNβ-TYRP1 therapy.