CD176 single-chain variable antibody fragment inhibits the adhesion of cancer cells to endothelial cells and hepatocytes

Abstract

CD176 (Thomsen-Friedenreich antigen) is a tumor-associated carbohydrate epitope (glycotope) functionally involved in blood spread and liver metastasis of cancer cells by mediating the adhesion of cancer cells to endothelial cells and hepatocytes, respectively. CD176 could be a promising target for antitumor immunotherapy. We applied B lymphocytes obtained from mice immunized with CD176 antigen and constructed a phage display library. A positive clone of CD176 single-chain variable antibody fragment (scFv) was successfully screened from this library. The CD176 scFv was expressed in Escherichia coli and purified. The purified scFv can bind to the natural CD176 expressed on the surface of cancer cells. Furthermore, the CD176 scFv inhibits the adhesion of CD176⁺ cancer cells to endothelial cells and hepatocytes. This CD176 scFv provides a basis for future development of recombinant CD176-specific antibodies that can be used in therapeutic application.

Keywords

CD176 / Thomsen-Friedenreich antigen / scFv / cancer / therapy / adhesion / metastasis

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Acknowledgements

This work was supported by National Natural Science Foundation of China (No. 81072563) and the Chinese Academy of Sciences (KSCX2-YW-R-196). We especially thank Dr. Reinhard Schwartz-Albiez (German Cancer Research Center, Heidelberg, Germany) for his support and valuable critical comments.

Compliance with ethics guidelines

Jiangnan Liu, Bin Yi, Zhe Zhang, and Yi Cao declare that they have no conflict of interests. All institutional and national guidelines for the care and use of laboratory animals were followed.

Electronic Supplementary Material Supplementary material is available in the online version of this article at http://dx.doi.org/10.1007/s11684-016-0443-1 and is accessible for authorized users.

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