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

Abstract

Background: Prostate 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. Results: Antibody 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. Conclusions: Antibody 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.