Abstract
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.
Highlights
Prostate cancer is the most-diagnosed non-skin cancer among males in the US, and the second leading cause of cancer-related death
In addition to non-specific therapeutics, prostate cancer diagnosis using prostate specific antigen (PSA) blood levels is no longer recommended for use by the United States Preventive Services Task Force (USPSTF) [9,10,11,12,13]
Antibody fragment screening In order to obtain androgen-dependent prostate cancer cell-specific antibody fragments, seven rounds of screening and enrichment were completed with a yeastdisplayed singlechain Fragment variable (scFv) library [23] (Figure 1, Table 1)
Summary
Prostate cancer is the most-diagnosed non-skin cancer among males in the US, and the second leading cause of cancer-related death. Prostate cancer is the most-diagnosed non-skin cancer in the United States, with an estimated 233,000 new diagnoses in 2014 alone [1] It is the second leading cause of cancer-related deaths among males in the U.S, with an estimated 29,480 mortalities in 2014 [1]. The scope of this disease portends the necessity in developing improved clinical tools for its treatment. It is necessary to develop targeted therapeutics and diagnostics to further aid in treatment of prostate cancer. Therapeutic side effects can be serious and leave the possibility for recurrence in a more aggressive, androgen-independent
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