title: Structure-based development and optimization of therapy antibody drugs against TNFα.
abstract: Previously, we reported on the crystal structures of the Fab fragments of two food and drug administration approved therapeutic antibodies, Infliximab and Adalimumab, in complex with TNFα. The structurally identified epitopes on TNFα reveal the mechanism of TNFα inhibition by partially overlapping with the TNFα-receptor interface. In this study, we launched a screen of a phage display library to isolate novel anti-TNFα antibodies based on the adalimumab epitope. Structural analysis, the phage display antibody isolation technology, step-by-step antibody optimization, complementarity-determining region residues random mutagenesis, phage ELISA, binding affinity characterization, and cell signaling assays were used for the development and optimization of the novel anti-TNFα antibodies. Moreover, one of the novel antibodies, hAta09, has a superior inhibitory effect on TNFα function and signaling. Taken together, our report established that the novel anti-TNFα antibody hAta09 may achieve clinical efficacy in a TNFα-associated disease.
authors.affiliation: Key Laboratory of Oncology, Cancer Center, Chinese PLA General Hospital and Chinese PLA Medical School, Beijing, People's Republic of China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Fu
authors.forename: Xiaoze
authors.initials: X
authors.lastname: Wang
authors.forename: Weili
authors.initials: W
authors.lastname: Yang
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takeda
authors.forename: Shi
authors.initials: S
authors.lastname: Hu
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Lou
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.forename: Augus N
authors.initials: AN
authors.lastname: Bethune
authors.forename: Yajun
authors.initials: Y
authors.lastname: Guo