Developing Anti-EGFR/Anti-HER2 Bifunctional Antibody for Solid Tumors by Protein Engineering

Area of Science:

• Oncology
• Immunology
• Molecular Biology

Background:

• Overexpression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) is prevalent in various solid tumors, contributing to cancer progression and therapeutic resistance.
• Current monotherapies are often insufficient for complete tumor suppression, especially in cases of EGFR/HER2 co-amplification, necessitating advanced therapeutic strategies.

Purpose of the Study:

• To develop and characterize a bispecific antibody engineered for simultaneous targeting of EGFR and HER2.
• To evaluate the efficacy of this bispecific antibody in vitro, comparing it with monospecific antibodies.

Main Methods:

• Engineering of a bispecific anti-EGFR/HER2 antibody using knob-into-hole and CrossMab technologies.
• In vitro validation of dual-binding capacity and comparative assessment of anti-proliferative and pro-apoptotic effects against tumor cells expressing EGFR/HER2.

Main Results:

• The engineered bispecific antibody demonstrated effective dual-binding to both EGFR and HER2 extracellular domains.
• In vitro studies showed that the bispecific antibody significantly outperformed monospecific antibodies in inhibiting tumor cell proliferation.
• A notable increase in apoptotic markers was observed in tumor cells treated with the bispecific construct compared to monospecific treatments.

Conclusions:

• Bispecific antibodies targeting both EGFR and HER2 offer a promising therapeutic strategy with synergistic potential.
• This dual-targeting approach can overcome limitations of current monotherapies and contribute to combating drug resistance in EGFR/HER2-driven cancers.