Generation of a Fully Human scFv that binds Tumor-Specific Glycoforms

Abstract

Tumor-specific glycosylation changes are an attractive target for the development of diagnostic and therapeutic applications. Periostin is a glycoprotein with high expression in many tumors of epithelial origin including ovarian cancer. Strategies to target the peptide portion of periostin as a diagnostic or therapeutic biomarker for cancer are limited due to increased expression of periostin in non-cancerous inflammatory conditions. Here, we have screened for antibody fragments that recognize the tumor-specific glycosylation present on glycoforms of periostin containing bisecting N-glycans in ovarian cancer using a yeast-display library of antibody fragments, while subtracting those that bind to the periostin protein with glycoforms found in non-malignant cell types. We generated a biotinylated form of a fully human scFv antibody (scFvC9) that targets the bisecting N-glycans expressed by cancer cells. Validation studies in vitro and in vivo using scFvC9 indicate this antibody can be useful for the development of diagnostic, imaging, and therapeutic applications for cancers that express the antigen.