Development of anti-PD-L1 antibody based on structure prediction of AlphaFold2

Frontiers in Immunology

Immunology

Kun Du¹  He Huang¹ 

[1] School of Chemical Engineering and Technology, Tianjin University, Tianjin, China;Frontiers Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), Tianjin University, Tianjin, China;

关键词: AlphaFold2;    artificial intelligence;    antibody;    programmed death-ligand 1;    programmed cell death protein 1;    cancer immunotherapy;   

DOI  :  10.3389/fimmu.2023.1275999

 received in 2023-08-11, accepted in 2023-10-11,  发布年份 2023

来源: Frontiers

【 摘 要 】

Accurate structural information plays a crucial role in comprehending biological processes and designing drugs. Indeed, the remarkable precision of the AlphaFold2 has facilitated significant advancements in predicting molecular structures, encompassing antibodies and antigens. This breakthrough has paved the way for rational drug design, ushering in new possibilities in the field of pharmaceutical development. Within this study, performing analysis and humanization guided by the structures predicted by AlphaFold2. Notably, the resulting humanized antibody, h3D5-hIgG1, demonstrated exceptional binding affinity to the PD-L1 protein. The KD value of parental antibody 3D5-hIgG1 was increased by nearly 7 times after humanization. Both h3D5-hIgG1 and 3D5-hIgG1 bound to cells expressing human PD-L1 with EC50 values of 5.13 and 9.92nM, respectively. Humanization resulted in a twofold increase in the binding capacity of the antibody, with h3D5-hIgG1 exhibiting superior performance compared to the parental antibody 3D5-hIgG1. Furthermore, h3D5-hIgG1 promoted cytokine secretion of T cells, and significantly suppressed MC38-hPD-L1 tumor growth. This study highlights the potential for artificial intelligence-assisted drug development, which is poised to become a prominent trend in the future.

【 授权许可】

Unknown   
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