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Sensing antibody functions with a novel CCR8-responsive engineered cell
Jianyu Hao1, Yitong Lv1, Xufeng Xiao2
1College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Abstract:
Human chemokine receptor 8 (CCR8) is a promising drug target for immunotherapy of cancer and autoimmune diseases. Monoclonal antibody-based CCR8 targeted treatment shows significant inhibition in tumor growth. The inhibition of CCR8 results in the improvement of antitumor immunity and patient survival rates by regulating tumor-resident regulatory T cells. Recently monoclonal antibody drug development targeting CCR8 has become a research hotspot, which also promotes the advancement of antibody evaluation methods. Therefore, we constructed a novel engineered customized cell line HEK293-cAMP-biosensor-CCR8 combined with CCR8 and a cAMP-biosensor reporter. It can be used for the detection of anti-CCR8 antibody functions like specificity and biological activity, in addition to the detection of antibody-dependent cell-mediated cytotoxicity and antibody-dependent-cellular-phagocytosis. We obtained a new CCR8 mAb 22H9 and successfully verified its biological activities with HEK293-cAMP-biosensor-CCR8. Our reporter cell line has high sensitivity and specificity, and also offers a rapid kinetic detection platform for evaluating anti-CCR8 antibody functions.
Insights
A new cell line aids in evaluating anti-CCR8 antibody therapies for cancer and autoimmune diseases. This reporter system offers sensitive and specific detection of antibody functions, improving drug development.
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.
