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


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.


CONCLUSIONS
These results indicate that NRI shows potential as an agent in the treatment of mesotheliomas.
Adachi
Yasuo
Y
Laboratory of Immune Regulation, Wakayama Medical University, 105 Saito Bio Innovation Center, 7-7-20, Saito-Asagi, Ibaraki-City, Osaka, 567-0085, Japan.
Yoshio-Hoshino
Naoko
N
Aoki
Chieko
C
Nishimoto
Norihiro
N
D000256:Adenoviridae / Q000235:genetics*; D000911:Antibodies, Monoclonal / Q000235:genetics / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D045744:Cell Line, Tumor; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D008654:Mesothelioma / Q000628:therapy*; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects*; D057127:Single-Chain Antibodies / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors* / Q000096:biosynthesis
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D019947:Receptors, Interleukin-6; D057127:Single-Chain Antibodies; D042461:Vascular Endothelial Growth Factor A; C502936:tocilizumab