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- Title
Development of a Human B7-H3-Specific Antibody with Activity against Colorectal Cancer Cells through a Synthetic Nanobody Library.
- Authors
Li, Jingxian; Zhou, Bingjie; Wang, Shiting; Ouyang, Jiayi; Jiang, Xinyi; Wang, Chenglin; Zhou, Teng; Zheng, Ke-wei; Wang, Junqing; Wang, Jiaqi
- 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.
- Subjects
CANCER cells; ANTIBODY-dependent cell cytotoxicity; COLORECTAL cancer; MONOCLONAL antibodies; IMMUNOGLOBULINS; STRUCTURAL stability; NUCLEOTIDE sequencing
- Publication
Bioengineering (Basel), 2024, Vol 11, Issue 4, p381
- ISSN
2306-5354
- Publication type
Article
- DOI
10.3390/bioengineering11040381