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

IF 1.4 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Acta biochimica Polonica Pub Date : 2024-04-29 eCollection Date: 2024-01-01 DOI:10.3389/abp.2024.12185

Jianyu Hao, Yitong Lv, Xufeng Xiao, Lidan Li, Changyuan Yu

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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.

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利用新型 CCR8 响应工程细胞感知抗体功能。

人类趋化因子受体 8（CCR8）是一种很有希望用于癌症和自身免疫性疾病免疫治疗的药物靶点。基于单克隆抗体的 CCR8 靶向治疗可显著抑制肿瘤生长。抑制 CCR8 可通过调节肿瘤驻留调节性 T 细胞，提高抗肿瘤免疫力和患者生存率。近年来，以 CCR8 为靶点的单克隆抗体药物开发成为研究热点，这也推动了抗体评价方法的进步。因此，我们构建了一种新型的工程定制细胞系 HEK293-cAMP-生物传感器-CCR8，它结合了 CCR8 和 cAMP 生物传感器报告基因。它可用于检测抗 CCR8 抗体的特异性和生物活性等功能，还可用于检测抗体依赖性细胞介导的细胞毒性和抗体依赖性细胞吞噬作用。我们获得了一种新的 CCR8 mAb 22H9，并用 HEK293-cAMP-生物传感器-CCR8 成功验证了它的生物活性。我们的报告细胞系具有高灵敏度和特异性，也为评估抗 CCR8 抗体功能提供了一个快速动力学检测平台。

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来源期刊

Acta biochimica Polonica 生物-生化与分子生物学

CiteScore

2.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Acta Biochimica Polonica is a journal covering enzymology and metabolism, membranes and bioenergetics, gene structure and expression, protein, nucleic acid and carbohydrate structure and metabolism.