These results suggest that our improved peptide vaccine technology provides a novel prophylaxis measure as well as therapy for HCC patients with TM4SF5-positive tumors.
TM4SF5-mediated EMT contributes to diverse cellular functions, leading to fibrotic phenotypes and initiating and maintaining tumors in primary and/or metastatic regions, in addition to its role in muscle development in zebrafish.
Tumor formation in nude mice injected with TM4SF5-expressing cells and the growth of cells expressing endogenous TM4SF5, but not of TM4SF5-null cells, was suppressed by treatment with TSAHC, but not by treatment with its analogs.
In addition, TM4SF5 expression was significantly associated with tumor size, vascular invasion, tumor differentiation, and tumor-node-metastasis stage.
In this study, TSAHC and two derivatives showed similar antagonistic activities against TM4SF5-mediated signaling and multilayer growth in vitro and anti-tumorigenic activity even in early stages of TM4SF5-mediated tumor formation in nude mice.
Robust production of TM4SF5-specific antibodies was induced by challenge with CT-26 cells and the tumor growth was significantly suppressed in the immunized mice.