Sensing antibody functions with a novel CCR8-responsive engineered cell.

Area of Science:

• Immunology
• Pharmacology
• Biotechnology

Background:

• Human chemokine receptor 8 (CCR8) is a key target for cancer and autoimmune disease immunotherapies.
• Monoclonal antibodies targeting CCR8 demonstrate significant tumor growth inhibition and improved antitumor immunity.
• Advancements in antibody evaluation methods are crucial for CCR8-targeted drug development.

Purpose of the Study:

• To develop a novel engineered cell line for evaluating anti-CCR8 antibody functions.
• To establish a sensitive and specific platform for assessing antibody specificity, biological activity, and effector functions.
• To validate the utility of the reporter cell line with a newly developed CCR8 monoclonal antibody.

Main Methods:

• Construction of a customized HEK293 cell line engineered with CCR8 and a cAMP-biosensor reporter.
• Utilizing the reporter cell line to detect anti-CCR8 antibody specificity and biological activity.
• Assessing antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP) using the reporter system.

Main Results:

• Successful development of the HEK293-cAMP-biosensor-CCR8 reporter cell line.
• Verification of biological activities of a new CCR8 monoclonal antibody (mAb 22H9) using the developed cell line.
• Demonstration of high sensitivity and specificity of the reporter cell line for evaluating anti-CCR8 antibodies.

Conclusions:

• The novel engineered cell line provides a robust platform for evaluating anti-CCR8 antibody functions.
• This reporter system facilitates rapid kinetic detection and characterization of antibody efficacy.
• The developed cell line supports the advancement of CCR8-targeted immunotherapies for cancer and autoimmune diseases.