@article{APS10926,
author = {Hua-ying Li and Yi-li Chen and Xiang-nan Deng and Huan-huan Li and Jie Tan and Guo-jian Liu and Yu-juan Zheng and Min Pei and Kai-ting Peng and Li-li Yue and Xiao-jia Chen and Yu Liu and Yong-shan Zhao and Chun-he Wang},
title = {Bispecific antibody targeting both B7-H3 and PD-L1 exhibits superior antitumor activities},
journal = {Acta Pharmacologica Sinica},
volume = {44},
number = {11},
year = {2023},
keywords = {},
abstract = {Clinical application of PD-1 and PD-L1 monoclonal antibodies (mAbs) is hindered by their relatively low response rates and the occurrence of drug resistance. Co-expression of B7-H3 with PD-L1 has been found in various solid tumors, and combination therapies that target both PD-1/PD-L1 and B7-H3 pathways may provide additional therapeutic benefits. Up to today, however, no bispecific antibodies targeting both PD-1 and B7-H3 have reached the clinical development stage. In this study, we generated a stable B7-H3×PD-L1 bispecific antibody (BsAb) in IgG1-VHH format by coupling a humanized IgG1 mAb against PD-L1 with a humanized camelus variable domain of the heavy-chain of heavy-chain antibody (VHH) against human B7-H3. The BsAb exhibited favorable thermostability, efficient T cell activation, IFN-γ production, and antibody-dependent cell-mediated cytotoxicity (ADCC). In a PBMC humanized A375 xenogeneic tumor model, treatment with BsAb (10 mg/kg, i.p., twice a week for 6 weeks) showed enhanced antitumor activities compared to monotherapies and, to some degree, combination therapies. Our results suggest that targeting both PD-1 and B7-H3 with BsAbs increases their specificities to B7-H3 and PD-L1 double-positive tumors and induces a synergetic effect. We conclude that B7-H3×PD-L1 BsAb is favored over mAbs and possibly combination therapies in treating B7-H3 and PD-L1 double-positive tumors.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/10926}
}