AUTHOR=Cui Xiaopei , Jia Huifeng , Xin Hong , Zhang Lei , Chen Shi , Xia Simin , Li Xue , Xu Wei , Chen Xiaofang , Feng Yujie , Wei Xiaoyue , Yu Haijia , Wang Yanting , Zhan Yifan , Zhu Xiangyang , Zhang Xuemei TITLE=A Novel Bispecific Antibody Targeting PD-L1 and VEGF With Combined Anti-Tumor Activities JOURNAL=Frontiers in Immunology VOLUME=12 YEAR=2021 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.778978 DOI=10.3389/fimmu.2021.778978 ISSN=1664-3224 ABSTRACT=

Therapeutic monoclonal antibodies (mAbs) blocking immune checkpoints have been mainly used as monotherapy. Recently, combination therapy targeting multiple immune checkpoints has recently been explored to increase anti-cancer efficacy. Particularly, a single molecule targeting more than one checkpoints has been investigated. As dual blocking of PD-1/PD-L1 and VEGF/VEGFR has demonstrated synergism in anti-tumor activities, we developed a novel bispecific antibody, termed HB0025, which is formed via fusing the domain 2 of vascular endothelial growth factor receptor 1 (VEGFR1D2) and anti-PD-L1 mAb by using mAb-Trap technology. HB0025 almost completely retains the binding affinities and the biological activities in-vitro when compared with the parent anti-PD-L1 mAb or VEGFR1D2 fusion protein. Preclinical data demonstrated that HB0025 was more effective in inhibiting cancer growth than anti PD-L1 mAb or VEGFR1D2 fusion protein. Thus, our bispecific antibody may bring about greater clinical benefits and broader indications.