Rhamnose modified antibodies show improved immune killing towards EGFR-positive solid tumor cells

Area of Science:

• Immunology
• Oncology
• Biotechnology

Background:

• Therapeutic monoclonal antibodies (mAbs) targeting the epidermal growth factor receptor (EGFR) are effective against colorectal and other solid cancers.
• Enhancing effector functions of anti-EGFR mAbs is a key strategy for improving clinical efficacy.

Purpose of the Study:

• To develop an effector function-enhanced antibody through rhamnose (Rha) functionalization.
• To investigate the impact of Rha conjugation on the anti-tumor activity of cetuximab, an anti-EGFR mAb.

Main Methods:

• Site-specific conjugation of rhamnose (Rha) haptens to cetuximab.
• Evaluation of cetuximab-Rha conjugate's ability to redirect endogenous anti-Rha antibodies to EGFR-positive tumor cells.
• Assessment of enhanced effector functions, including complement-dependent cytotoxicity (CDC) and antibody-dependent cell-mediated phagocytosis (ADCP).

Main Results:

• Cetuximab-Rha conjugate successfully redirected endogenous antibodies to EGFR-positive tumor cells.
• Significant enhancement of effector functions, particularly complement-dependent cytotoxicity (CDC), which was previously inactive in cetuximab.
• Demonstrated improved antibody-dependent cell-mediated phagocytosis (ADCP).

Conclusions:

• Rhamnose functionalization is a viable strategy to enhance the effector functions of therapeutic antibodies like cetuximab.
• The developed rhamnose-modified antibody shows potential for improved immunotherapy of EGFR-positive solid tumors.
• This approach offers a novel method to boost the efficacy of existing antibody-based cancer therapies.