Identification of an antibody fragment specific for androgen-dependent prostate cancer cells

BMC Biotechnology

Research Article

Sara Nayeem¹  Letha J Sooter¹  Ryan M Williams²  Cyrus J Hajiran³ 

[1] Department of Basic Pharmaceutical Sciences, West Virginia University, PO Box 9530, 1 Medical Center Drive, 26506, Morgantown, WV, USA;Department of Basic Pharmaceutical Sciences, West Virginia University, PO Box 9530, 1 Medical Center Drive, 26506, Morgantown, WV, USA;Memorial Sloan Kettering Cancer Center, Molecular Pharmacology & Chemistry Program, 1275 York Ave., 10065, New York, NY, USA;Department of Biology, West Virginia University, PO Box 6057, 53 Campus Drive, 26506, Morgantown, WV, USA;

关键词: Prostate cancer;    Antibody fragment;    scFv;    Library screening;    Yeast;   

DOI  :  10.1186/1472-6750-14-81

 received in 2014-05-12, accepted in 2014-08-29,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundProstate cancer is the most-diagnosed non-skin cancer among males in the US, and the second leading cause of cancer-related death. Current methods of treatment and diagnosis are not specific for the disease. This work identified an antibody fragment that binds selectively to a molecule on the surface of androgen-dependent prostate cancer cells but not benign prostatic cells.ResultsAntibody fragment identification was achieved using a library screening and enrichment strategy. A library of 109 yeast-displayed human non-immune antibody fragments was enriched for those that bind to androgen-dependent prostate cancer cells, but not to benign prostatic cells or purified prostate-specific membrane antigen (PSMA). Seven rounds of panning and fluorescence-activated cell sorting (FACS) screening yielded one antibody fragment identified from the enriched library. This molecule, termed HiR7.8, has a low-nanomolar equilibrium dissociation constant (Kd) and high specificity for androgen-dependent prostate cancer cells.ConclusionsAntibody fragment screening from a yeast-displayed library has yielded one molecule with high affinity and specificity. With further pre-clinical development, it is hoped that the antibody fragment identified using this screening strategy will be useful in the specific detection of prostate cancer and in targeted delivery of therapeutic agents for increased efficacy and reduced side effects.

【 授权许可】

Unknown   
© Williams et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.