Creation of a new drug with a bispecific antibody against mesenchymal tissue

2014 Fiscal Year Final Research Report

• Project/Area Number: 24680093
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: 独立行政法人医薬基盤研究所
• Principal Investigator: KAMADA Haruhiko 独立行政法人医薬基盤研究所, 創薬基盤研究部, サブプロジェクトリーダー (00324509)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 分子標的治療 / 二重特異性抗体 / 乳がん / CD3 / EphA10

Outline of Final Research Achievements

In our efforts to develop a new bispecific monoclonal antibody drug against breast cancer, we attempted to generate a tandem single-chain variable fragment (taFv) targeting both the T-cell CD3 antigen and Ephrin receptor A10 (EphA10), which were previously identified as breast cancer novel biomarker proteins. We constructed the taFv (EphA10/CD3) expression vector that contain two single chain Fv (scFv) joined by linker. The taFv was expressed transiently and verified for identity by Western blot analysis. By flow cytometry analysis, each monomer and dimer bound both antigens EphA10 and CD3. The taFvs showed highly cytotoxicity specifically against EphA10 over-expression cancer cell line. Most notably, the cytotoxicity of taFv dimer was higher than taFv monomer at low Effector/Target ratio and low concentration. This taFv (EphA10/CD3) could induce EphA10 specific cytotoxicity. And also, this BsAb showed the therapeutic effects against EphA10-expressing tumor cells in vivo.

Free Research Field

タンパク質工学