Challenge to the development of small tetraspecific and tetravalent antibody as innovative cancer therapeutic antibodies

2015 Fiscal Year Final Research Report

• Project/Area Number: 25640085
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Tumor therapeutics
• Research Institution: Tokyo University of Agriculture and Technology (2015); Tohoku University (2013-2014)
• Principal Investigator: ASANO Ryutaro 東京農工大学, 工学(系)研究科(研究院), 准教授 (80323103)
• Co-Investigator(Kenkyū-buntansha): UMETSU Mitsuo 東北大学, 大学院工学研究科, 教授 (70333846)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 癌 / 蛋白質 / バイオテクノロジー / 生物・生体工学 / 四重特異性四価抗体

Outline of Final Research Achievements

Although small bispecific antibodies are attractive molecules, their decreases in binding valency and in vivo half-life are left as a problem. Multimerization of small antibodies is one strategy to solve these drawbacks. In this study using four kinds of antibody fragments, we tried to develop small tetraspecific and tetravalent cancer therapeutic antibodies to regulate multimeric structure and to enhance therapeutic efficacy. We couldn’t obtain the functional molecules in bacterial expression system; however, we successfully prepared tetraspecific and tetravalent antibodies with high therapeutic effects in mammalian expression system. Further, our results showed that Fc fusion to facilitate their purification causes decreases in their cytotoxic effects.

Free Research Field

応用生物工学