VEGF targeting in mesotheliomas using an interleukin-6 signal inhibitor based on adenovirus gene delivery

Abstract

Background: Malignant mesotheliomas reportedly secrete interleukin-6 (IL-6) which augments production of vascular endothelial growth factor (VEGF) from mesothelioma cells. We previously reported the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody. Since NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. In this study, we report VEGF targeting through NRI expression based on adenovirus-mediated gene delivery in mesothelioma cells.

Materials and methods: We constructed an NRI expression vector in the context of a tropism-modified adenovirus vector that had enhanced infectivity in mesothelioma cells.

Results: This virus effectively induced NRI secretion from mesothelioma cells. This virus infection also reduced the VEGF production in mesothelioma cells.

Conclusion: These results indicate that NRI shows potential as an agent in the treatment of mesotheliomas.