Selection for Anti-transferrin Receptor Bispecific T-cell Engager in Different Molecular Formats

• 作者: Guan-xin SHEN Hong-ling TANG Hui-fen ZHU Ming-peng FU Ping LEI Yong HE Zi-long GUO
• 来源期刊: 当代医学科学(英文)
• 学科: 医学
• 关键词: bispecific antibody single-chain tandem single-chain variable fragments DIABODY transferrin receptor CD3
• 年，卷（期）: 2020,（1）
• 页码范围: 28-34
• 页数: 7页
• 分类号: R73

摘要

Selecting an ideal molecular format from diverse structures is a major challenge in developing a bispecific antibody(BsAb).To choose an ideal format of anti-CD3 x anti-transferrin receptor(TfR)bispecific antibodies for clinical application,we constructed TfR bispecific T-cell engager(BiTE)in two extensively applied formats,including single-chain tandem singlechain variable fragments(scFvs)and double-chain diabodies,and evaluated their functional characterizations in vitro.Results demonstrated that TfR-BiTE in both formats directed potent killing of TfR+HepG2 cells.However,compared to two・chain diabodies,scFvs were more efficient in antigen binding and TfR target killing.Furthermore,different domain orders in scFvs would also be evaluated because single-TfR-CD3-His was preferable to single-CD3-TfR-His in immunotherapeutic strategies.Thus,the single-chain tandem TfR-CD3 format was favored for further investigation in cancer therapy.