Improvement of the multi-specificity for anti-IDH1/2 mAb MsMab-1 and 2 based on structure

• Project/Area Number: 26840015
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Structural biochemistry
• Research Institution: Tohoku University
• Principal Investigator: Ogasawara Satoshi 東北大学, 医学(系)研究科(研究院), 助教 (30546685)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: モノクローナル抗体 / 多重特異性 / X線結晶構造解析

Outline of Final Research Achievements

We tried to solve the crystal structure of MsMab-1 and 2. We identified a critical amino acid residue for the multi-specificity from the crystal structure of MsMab-1. Hence MsMab-1 was mutated the amino acid residue of antigen recognition site based on the structure. Mutated MsMab-1 was changed the specificity against mutated IDH1/2. MsMab-2 was not able to try a crystallization experiment for its low level of productivity.
We generated a novel multi-specific anti-IDH1/2 monoclonal antibody MsMab-3, which could bind mutated IDH1/2 peptides but not mutated IDH1/2 proteins.