Development of new antiprotozoal therapy using molecules that recruit immune cells

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K19201
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Research Field: Biomolecular chemistry and related fields
• Research Institution: Osaka University
• Principal Investigator: Fukase Koichi 大阪大学, 理学研究科, 教授 (80192722)
• Research Collaborator: MANABE Yoshiyuki
• Project Period (FY): 2017-06-30 – 2019-03-31
• Keywords: 糖鎖 / 免疫 / 抗体

Outline of Final Research Achievements

Antibody drugs are one of the most important molecular targeted drugs having high specificity. Conversely, their insufficient efficacy has been a critical issue in many cases. Here, we developed α-gal antibody conjugates as next-generation antibody drugs. α-Gal, Galα1-3Galβ1-4GlcNAc, is widely expressed in nature, but humans do not have this trisaccharide. Instead, humans have large amounts of antibodies against α-gal (anti-Gal antibodies, 1-2% of total serum IgG and 3-8% of total IgM), which cause an acute immune response, such as hyperacute rejection induced by xenotransplantation from pig to baboon. Therefore, α-gal antibody conjugates can show strong cytotoxicity by recruiting anti-Gal antibodies. Many antibody drugs exhibit a low response rate. Moreover, a number of antibodies have failed in clinical trials due to low potency. We expect that our method will enable re-development of therapeutic antibodies and their candidates to improve potency.

Free Research Field

天然物化学，ケミカルバイオロジー，糖質化学

Academic Significance and Societal Importance of the Research Achievements

本研究では、がん抗体とα-galエピトープを複合化し、がんに対して自然抗体をリクルートし、抗体の細胞障害活性を大幅に向上させることに成功した。本手法の適用範囲は極めて広く、がんに限らず、ウイルスや原虫などの感染症に対しても有効であることが期待される。現在、抗体は医薬品の主流となっているが、その効果が十分でないものも多い。また、抗体医薬品の開発途中でドロップしたものも多い。これらの抗体に対して本コンセプトを適用することで、有効な治療法を提供しうる。加えて、糖鎖を利用してがん細胞に対して急性拒絶反応を起こすというコンセプトは、新たな免疫療法の可能性を示すもので、学術的な新規性、独創性も高い。