2019 Fiscal Year Final Research Report

A novel immunotherapy for advanced renal cell carinoma by glycobiological interaction with natural killer cells

Research Project

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Project/Area Number	17K07210
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Tumor therapeutics
Research Institution	Tohoku University
Principal Investigator	Kawasaki Yoshihide 東北大学, 大学病院, 講師 (80722256)
Co-Investigator(Kenkyū-buntansha)	荒井陽一東北大学, 医学系研究科, 名誉教授 (50193058) 佐藤信東北大学, 医学系研究科, 非常勤講師 (70282134) 伊藤明宏東北大学, 医学系研究科, 教授 (70344661) 三塚浩二東北大学, 医学系研究科, 准教授 (80568171) 泉秀明東北大学, 医学系研究科, 非常勤講師 (80722545) 嶋田修一東北大学, 大学病院, 助教 (80749218) 佐藤琢磨東北大学, 医学系研究科, 助教 (80804856)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	腎細胞癌 / DSGb5 / NK細胞 / 精密定量測定 / 免疫治療
Outline of Final Research Achievements	We reported new immunotherapy with activated NK cells therapy by regulating glycoantigen DSGb5 on renal cancer cells. However, when there was small expression of DSGb5 of tumor we found that anticancer effect by activated NK cells was so restricted. We faced difficult task to quantify DSGb5 expressing on renal cancer cells to select the patients adaptable to activated NK cells therapy. Therefore, we needed to quantify glycoatnigen DSGb5 on renal cancer cells. DSGb5 consists of carbohydrate chain and sphingolipid which have variety of fatty acids. First of all, we estimated expression level of DSGb5 by calculating 8 fatty acids with 16 carbons to 26 carbons. However, standard substance of DSGb5 were necessary to accurate quantify DSGb5 of tumor. And then we established experimental system of chemical synthesis of DSGb5, at last we were able to synthase DSGb5 chemically to accurate quantify by mass spectrometer.
Free Research Field	腎細胞癌診断治療
Academic Significance and Societal Importance of the Research Achievements	糖鎖生物学的な観点からNK細胞におけるimmune check point阻害を解析する点に、学術的な特色・特徴があるものと考える。また、vitroではすでにDSGb5とSiglec-7とのinteractionの抑制により、NK細胞の殺細胞効率の上昇が得られていることから、われわれが提案する新規治療薬が臨床の場において、これまでの治療薬に加え、さらなる抗腫瘍効果が得られる予想している。この研究の結果が切除不能腎癌患者のQOLの向上と、予後のさらなる延長をもたらす可能性があることに意義があるものと考える。