2013 Fiscal Year Final Research Report

Analysis for the anti-tumor effect of STAT3 inhibitor (rR9-GRIM19) against tumor-bearing host

Research Project

Project/Area Number	24791145
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Dermatology
Research Institution	University of Yamanashi
Principal Investigator	HANAWA Fumie 山梨大学, 医学部附属病院, 助教 (80535592)
Project Period (FY)	2012-04-01 – 2014-03-31
Keywords	皮膚科学 / 皮膚腫瘍学
Research Abstract	Crosstalk between cancer cells and immune cells in established cancer microenvironment leads to the restriction of immune responses via phosphorylated STAT3 (pSTAT3). To inhibit STAT3-mediated signaling cascades in cancer microenvironment, we generated rR9-GRIM19 fusion proteins. To elicit complete B16 regression, we investigated the antitumor effects of combination immunotherapies with rR9-GRIM19. rR9-GRIM19 elicited enhanced antitumor effects when combined either with rR9-OVA (as our Th1/Tc1-inducible adjuvant) or CpG-ODN, but only the combination of CpG-ODN, rR9-OVA, and rR9-GRIM19 (COG therapy) elicited complete B16 tumor regression. Interestingly, melanoma-specific cytotoxic T lymphocyte (CTL) expansion with IFN-g production occurred in COG-treated B16-bearing. our results indicate that strong antitumor effects could be elicited when the cancer microenvironment was simultaneously exposed with STAT3 inhibitor and STAT1 activator (Tc1/Th1-inducible adjuvants).