Structure and activity of an anti-epidermal growth factor receptor antibody without galactose-α-1,3-galactose...

Area of Science:

• Oncology
• Immunology
• Biotechnology

Background:

• Epidermal growth factor receptor (EGFR) is a key target in cancer therapy.
• Approved anti-EGFR antibodies can cause hypersensitivity reactions due to the galactose-α-1,3-galactose (α-Gal) structure, often present in insect cell expression systems.

Purpose of the Study:

• To develop a novel anti-EGFR monoclonal antibody (AB01) with simplified glycosylation patterns to mitigate hypersensitivity reactions.
• To compare the efficacy and characteristics of AB01 with cetuximab, a currently approved anti-EGFR antibody.

Main Methods:

• Utilized Chinese hamster ovary (CHO) cells for the production of monoclonal antibody AB01.
• Performed comparative analyses of molecular weight, secondary structure, binding affinity, and endocytosis behavior between AB01 and cetuximab.
• Assessed cell proliferation inhibition and cell cycle effects using flow cytometry.

Main Results:

• AB01 exhibited distinct glycotypes compared to cetuximab, while maintaining similar molecular weight, secondary structure, binding affinity, and endocytosis.
• Flow cytometry revealed that AB01 induces G1 cell cycle arrest, inhibiting cancer cell proliferation.
• Both AB01 and cetuximab demonstrated comparable sensitivity across all tested cancer cell lines.

Conclusions:

• AB01, produced with simplified glycosylation in CHO cells, represents a potential anti-EGFR therapeutic candidate.
• The distinct glycosylation pattern of AB01 may reduce the risk of α-Gal-induced hypersensitivity reactions.
• AB01 shows comparable anti-cancer efficacy to cetuximab, suggesting its viability for clinical application.