We conclude that TANVΔ66R/mIL-2 is potentially therapeutic for human melanomas in the absence of T cells, and IL-2 expression resulted in an overall increase of therapeutic efficacy.

Neuregulin (NRG), an epidermal growth factor is known to promote the growth of various cell types, including human melanoma cells through ErbB family of tyrosine kinases receptors. Tanapoxvirus (TPV) encoded protein TPV-15L, a functional mimic of NRG, also acts through ErbB receptors. Here, we show that the TPV-15L protein promotes melanoma proliferation. TPV recombinant generated by deleting the 15L gene (TPVΔ15L) showed replication ability similar to that of wild type TPV (wtTPV) in owl monkey kidney (OMK) cells, human lung fibroblast (WI-38) cells and human melanoma (SK-MEL-3) cells. Whereas, a TPV recombinant with both 15L and the thymidine kinase (TK) gene (66R) ablated (TPVΔ15LΔ66R) replicated less efficiently than TPVΔ15L and the parental virus. TPVΔ15L exhibited more robust tumor-regression in the melanoma-bearing nude mice than other TPV recombinants. Our results indicate that deletion of TPV-15L gene product which facilitates the growth of human melanoma cells can be an effective strategy to enhance the oncolytic potential of TPV for the treatment of melanoma.