AUTHOR=Hao Jianyu , Lv Yitong , Xiao Xufeng , Li Lidan , Yu Changyuan TITLE=Sensing antibody functions with a novel CCR8-responsive engineered cell JOURNAL=Acta Biochimica Polonica VOLUME=71 YEAR=2024 URL=https://www.frontierspartnerships.org/journals/acta-biochimica-polonica/articles/10.3389/abp.2024.12185 DOI=10.3389/abp.2024.12185 ISSN=1734-154X 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.