Tanapoxvirus lacking the 15L gene inhibits melanoma cell growth in vitro by inducing interferon-λ1 release

Oncolytic viruses (OVs) have emerged as a promising approach for melanoma treatment by causing tumor lysis and inducing immuno-modulatory activities. Tanapoxvirus (TPV), which causes a mild self-limiting disease in humans and contains a large DNA genome, appears as a promising OV candidate. TPV recombinants were generated with the thymidine kinase/66R gene deletion (TPVΔ66R), the 15L gene deletion (TPVΔ15L), or with both the 15L and 66R gene ablation (TPVΔ15LΔ66R). Our previous studies have shown that treatment of TPVΔ15L resulted in significant tumor regression in xenotransplanted human melanoma in nude mice. Here, we demonstrate that an anti-viral activity identified as interferon-λ1 (IFN-λ1) was secreted in a remarkably higher quantity from human lung fibroblast WI-38 and melanoma SK-MEL-3 cells infected with TPVΔ15L. Furthermore, we show that IFN-λ1 exhibits a more pronounced anti-proliferative effect in melanoma cells than IFN-α and IFN-β in vitro. Additional experiments strongly suggest that TPVΔ15L kills melanoma cells partially through inducing IFN-λ1. Taken together, our results demonstrate the immuno-modulatory activities associated with TPVΔ15L and suggest further exploration of TPVΔ15L as a melanoma virotherapy.