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

作　　者：Ming-peng FU Zi-long GUO Hong-ling TANG Hui-fen ZHU Guan-xin SHEN Yong HE Ping LEI 

机构地区：[1]Department of Immunology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China [2]Department of Nuclear Medicine and PET Center,Zhongnan Hospital of Wuhan University,Wuhan 430071,China

出　　处：《Current Medical Science》2020年第1期28-34,共7页当代医学科学（英文）

基　　金：National Natural Science Foundation of China(No.31570937 and No.81871391);Natural Science Foundation of Hubei Province of China(No.2017CFB707);the Fundamental Research Funds for the Central Universities of China(No.HUST:2018KFYYXJJ086);Graduates'Innovation Foundation of Huazhong University of Science and Technology(No.5003510001).

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.

关 键 词：bispecific antibody single-chain tandem single-chain variable fragments DIABODY transferrin receptor CD3 

分 类 号：R73[医药卫生—肿瘤]