Oncolytic tanapoxvirus expressing interleukin-2 is capable of inducing the regression of human melanoma tumors in the absence of T cells.

In this study, a recombinant TANV expressing mouse IL-2 (TANVΔ66R/mIL-2) was generated, where the viral thymidine kinase (TK) gene (66R) was replaced with the mIL-2 transgene. In cell culture, expression of IL-2 attenuated virus replication of not only TANVΔ66R/mIL-2, but also TANVGFP when co-infecting with TANVΔ66R/mIL-2. Further, we demonstrate that IL-2 inhibits virus replication through intracellular components and without activating the interferon-signaling pathway. The anti-tumor potential of TANVΔ66R/mIL-2 was studied in athymic nude mice carrying human melanoma xenografts. Introduction of mIL-2 into TANV remarkably increased its anti-tumor activity, resulting in a more significant regression than with wild-type (wt) TANV and TANVΔ66R. Histopathological studies showed that more extensive cell degeneration with a significantly increased peri-tumor accumulation of mononuclear cells (some of which had a macrophage phenotype - F4/80) was present in the tumors treated with TANVΔ66R/mIL-2, compared with that in those treated with wtTANV or TANVΔ66R. Taken together, these results suggest that TANVΔ66R/mIL-2 is potentially therapeutic for human melanomas in the absence of T cells, and that IL-2 expression results in an overall increase of therapeutic efficacy despite its viral inhibitory effects. PMID: 28669340 [PubMed - as supplied by publisher]
Source: Current Cancer Drug Targets - Category: Cancer & Oncology Authors: Tags: Curr Cancer Drug Targets Source Type: research