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建立一种新型抗鼠 CCR1 单克隆抗体 CMab-6.

Establishment of a Novel Anti-Mouse CCR1 Monoclonal Antibody CMab-6.

机构信息

Department of Antibody Drug Development, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

Monoclon Antib Immunodiagn Immunother. 2024 Apr;43(2):67-74. doi: 10.1089/mab.2023.0032. Epub 2024 Mar 21.

DOI:10.1089/mab.2023.0032
PMID:38512465
Abstract

C-C motif chemokine receptor 1 (CCR1/CD191) is a member of G-protein-coupled receptors and is expressed on myeloid cells, such as neutrophils and macrophages. Because the CCR1 signaling promotes tumor expansion in the tumor microenvironment (TME), the modification of TME is an effective strategy for cancer therapy. Although CCR1 is an attractive target for solid tumors and hematological malignancies, therapeutic agents for CCR1 have not been approved. Here, we established a novel anti-mouse CCR1 (mCCR1) monoclonal antibody (mAb), CMab-6 (rat IgG, kappa), using the Cell-Based Immunization and Screening method. Flow cytometry and Western blot analyses showed that CMab-6 recognizes mCCR1 specifically. The dissociation constant of CMab-6 for mCCR1-overexpressed Chinese hamster ovary-K1 was determined as 3.9 × 10 M, indicating that CMab-6 possesses a high affinity to mCCR1. These results suggest that CMab-6 could be a useful tool for targeting mCCR1 in preclinical mouse models.

摘要

C-C 基序趋化因子受体 1(CCR1/CD191)是 G 蛋白偶联受体家族的成员,表达于髓系细胞,如中性粒细胞和巨噬细胞。由于 CCR1 信号促进肿瘤微环境(TME)中的肿瘤扩张,因此修饰 TME 是癌症治疗的有效策略。尽管 CCR1 是实体瘤和血液恶性肿瘤的一个有吸引力的靶点,但针对 CCR1 的治疗剂尚未获得批准。在这里,我们使用基于细胞的免疫和筛选方法建立了一种新型抗小鼠 CCR1(mCCR1)单克隆抗体(mAb)CMab-6(大鼠 IgG,kappa)。流式细胞术和 Western blot 分析表明,CMab-6 特异性识别 mCCR1。CMab-6 与过表达 mCCR1 的中国仓鼠卵巢-K1 的解离常数为 3.9×10 M,表明 CMab-6 对 mCCR1 具有高亲和力。这些结果表明,CMab-6 可能成为在临床前小鼠模型中靶向 mCCR1 的有用工具。

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