Regulation of glycan-dependent cytotoxicity against advanced HCC by the molecular target drug

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08945
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Toho University
• Principal Investigator: HIGAI Koji 東邦大学, 薬学部, 准教授 (70297711)
• Co-Investigator(Kenkyū-buntansha): 永井 英成 東邦大学, 医学部, 准教授 (30349899)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: NK細胞 / 分子標的薬 / 肝細胞がん

Outline of Final Research Achievements

In this study, we identified a transcriptional promoter region of hST3Gal3, the enzyme related biosynthesis of glycan ligands against KLRs, and ULBP-1 (protein-ligand of NKG2D).
Furthermore, we clarified that these molecules were regulated by sorafenib and that macrophage was directly activated by sorafenib. We quantitatively determined the concentration of sorafenib in sera obtained from patients with HCC. The lack of a correlation between serum levels of sorafenib and the orally administered dose in patients suggests that it may be critical to maintaining an effective drug concentration in plasma for a long period of time.

Free Research Field

肝細胞がん

Academic Significance and Societal Importance of the Research Achievements

本研究により進行性肝細胞がんを標的としたソラフェニブの新規作用と免疫系への影響を明らかにすることができた。この結果は、今後のNK細胞を利用した免疫療法に対して重要な知見が得られたものと考えられる。また、ソラフェニブを投与されたHCC患者におけるソラフェニブの血中濃度測定結果から、実臨床におけるソラフェニブの適正使用における血中濃度測定の重要さが示唆された。