title: Selection and characterization of human antibody fragments specific for psoriasin - a cancer associated protein.
abstract: S100A7 (psoriasin) is a calcium-binding protein that is upregulated in many types of cancer and often associated with poor prognosis. Its role in carcinogenesis has been associated with the stimulation of VEGF and EGF activity. The recent research showed that psoriasin directly interacts with αvβ6 integrin, a protein related to the invasive phenotype of cancer. Moreover, this interaction promotes the αvβ6-dependent invasive activity. The important function of S100A7 in carcinoma development determines a great need for valuable tools enabling its detection, quantification and also activity inhibition. Here, we show the selection of S100A7 specific antibody fragments from the human scFv phage library ETH-2 Gold. We have selected antibody fragments specific for psoriasin, purified them and analyzed by BIAcore affinity measurements. The best clone was subjected to affinity maturation procedure yielding molecule with a subnanomolar affinity towards human S100A7 protein. Selected clone was expressed in a bivalent format and applied for immunostaining analysis, which confirmed the ability of the antigen recognition in physiological conditions. We therefore propose that obtained antibody, that is the first phage display-derived human antibody against psoriasin, can serve as a useful psoriasin binding platform in research, diagnostics and therapy of cancer.
authors.affiliation: Faculty of Biotechnology, University of Wroclaw, Tamka 2, 50-137 Wroclaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Cyranka-Czaja
authors.forename: Sarah
authors.initials: S
authors.lastname: Wulhfard
authors.forename: Dario
authors.initials: D
authors.lastname: Neri
authors.forename: Jacek
authors.initials: J
authors.lastname: Otlewski
mesh_terms: D000912:Antibodies, Neoplasm / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*; D000915:Antibody Affinity; D014408:Biomarkers, Tumor / Q000276:immunology*; D006801:Humans; D009369:Neoplasms / Q000276:immunology*; D019151:Peptide Library; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000737:chemistry / Q000276:immunology / Q000302:isolation & purification*
chemical_list: D000912:Antibodies, Neoplasm; D014408:Biomarkers, Tumor; D019151:Peptide Library; D000075023:S100 Calcium Binding Protein A7; D009418:S100 Proteins; C089242:S100A7 protein, human; D057127:Single-Chain Antibodies