Development of a Human B7-H3-Specific Antibody with Activity against Colorectal Cancer Cells through a Synthetic Nanobody Library

Author:

Li Jingxian1,Zhou Bingjie1,Wang Shiting1,Ouyang Jiayi1,Jiang Xinyi1,Wang Chenglin2,Zhou Teng3ORCID,Zheng Ke-wei4,Wang Junqing1ORCID,Wang Jiaqi1ORCID

Affiliation:

1. School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China

2. Shenzhen Qiyu Biotechnology Co., Ltd., Shenzhen 518107, China

3. School of Cyberspace Security, Hainan University, Haikou 570228, China

4. School of Biomedical Sciences, Hunan University, Changsha 410082, China

Abstract

Nanobodies have emerged as promising tools in biomedicine due to their single-chain structure and inherent stability. They generally have convex paratopes, which potentially prefer different epitope sites in an antigen compared to traditional antibodies. In this study, a synthetic phage display nanobody library was constructed and used to identify nanobodies targeting a tumor-associated antigen, the human B7-H3 protein. Combining next-generation sequencing and single-clone validation, two nanobodies were identified to specifically bind B7-H3 with medium nanomolar affinities. Further characterization revealed that these two clones targeted a different epitope compared to known B7-H3-specific antibodies, which have been explored in clinical trials. Furthermore, one of the clones, dubbed as A6, exhibited potent antibody-dependent cell-mediated cytotoxicity (ADCC) against a colorectal cancer cell line with an EC50 of 0.67 nM, upon conversion to an Fc-enhanced IgG format. These findings underscore a cost-effective strategy that bypasses the lengthy immunization process, offering potential rapid access to nanobodies targeting unexplored antigenic sites.

Funder

Natural Science Foundation of China

Publisher

MDPI AG

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