Development of novel cancer immunotherapy utilizing hyperacute rejection induced by alpha-gal epitope

2015 Fiscal Year Final Research Report

• Project/Area Number: 26560447
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Chemical biology
• Research Institution: Osaka University
• Principal Investigator: Fukase Koichi 大阪大学, 理学(系)研究科(研究院), 教授 (80192722)
• Co-Investigator(Kenkyū-buntansha): MANABE Yoshiyuki 大阪大学, 大学院理学研究科, 助教 (00632093)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: がん免疫療法 / 抗体薬物複合体（ADC） / 糖鎖 / 糖鎖合成 / α-gal / がんワクチン / アジュバント

Outline of Final Research Achievements

The α-Gal epitope is composed of trisaccharide structure produced in most mammals, however humans are deficient in that structure. On the other hand, humans produce a large amount of anti-Gal antibodies that specifically interact with the α-Gal epitope. Therefore, if pig organ expressing α-Gal is transplanted to human, the organ is heavily injured by hyper acute rejection. The purpose of this research is the development of the novel cancer therapy utilizing the α-Gal / anti-Gal antibody interaction: hyperacute rejection to tumor cell is induced by the labeling of tumor cell with α-Gal.
First, efficient synthesis of α-Gal epitope was achieved via one-pot glycosylation using imidate glycosyl donor and thioglycoside. Synthesized α-Gal was conjugated with anti-CD20 antibody, which is specifically recognize lymphoma cell. Cytotoxic assay using this antibody drug conjugate is under investigation. We also investigated the utilization of α-Gal as an adjuvant.

Free Research Field

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