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

Area of Science:

• Biochemistry
• Oncology
• Immunology

Background:

• Tumor-specific glycosylation presents a target for cancer diagnostics and therapeutics.
• Periostin, a glycoprotein, is highly expressed in epithelial tumors like ovarian cancer.
• Targeting periostin's peptide is limited by its expression in non-cancerous inflammatory conditions.

Purpose of the Study:

• To screen for antibody fragments recognizing tumor-specific glycosylation on periostin in ovarian cancer.
• To develop a diagnostic and therapeutic strategy targeting cancer-specific glycoforms of periostin.

Main Methods:

• Utilized a yeast-display library to screen for antibody fragments.
• Focused on periostin glycoforms with bisecting N-glycans in ovarian cancer.
• Subtracted antibodies binding to non-malignant cell glycoforms.
• Generated a biotinylated single-chain variable fragment antibody (scFvC9).

Main Results:

• Identified scFvC9, a fully human antibody fragment targeting cancer-specific bisecting N-glycans on periostin.
• Demonstrated scFvC9's binding specificity to tumor-associated glycosylation.
• In vitro and in vivo validation confirmed scFvC9's utility.

Conclusions:

• scFvC9 is a promising tool for developing novel cancer diagnostics and therapeutics.
• The antibody targets tumor-specific glycosylation, overcoming limitations of targeting the periostin peptide alone.
• Potential applications include early cancer detection, imaging, and targeted therapy for cancers expressing the antigen.