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抗金黄地鼠 Podoplanin 单克隆抗体 281-mG-f 的研制。

Development of Monoclonal Antibody 281-mG-f Against Golden Hamster Podoplanin.

机构信息

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

Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.

出版信息

Monoclon Antib Immunodiagn Immunother. 2022 Dec;41(6):311-319. doi: 10.1089/mab.2021.0058. Epub 2022 Apr 27.

DOI:10.1089/mab.2021.0058
PMID:35483059
Abstract

Golden (Syrian) hamster () is a small animal model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Pathological analyses of the tissues are required to understand the pathogenesis of SARS-CoV-2 and the evaluation of therapeutic modalities, including neutralizing monoclonal antibodies (mAbs). However, mAbs that recognize the golden hamster-derived antigens and distinguish specific cell types, such as the pneumocytes, are limited. Podoplanin (PDPN) is an essential marker of lung type I alveolar epithelial cells, kidney podocytes, and lymphatic endothelial cells. In this study, an anti-Chinese hamster () PDPN mAb PMab-281 (IgG, kappa) was established using the Cell-Based Immunization and Screening (CBIS) method. A defucosylated mouse IgG version of PMab-281 (281-mG-f) was also developed. The 281-mG-f strongly recognized both the Chinese hamster and the golden hamster PDPN using flow cytometry and could detect lung type I alveolar epithelial cells, lymphatic endothelial cells, and Bowman's capsules in the kidney from the golden hamster using immunohistochemistry. These results suggest the usefulness of 281-mG-f for analyzing the golden hamster-derived tissues and cells for SARS-CoV-2 research.

摘要

金黄地鼠()是严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染的小型动物模型。需要对组织进行病理学分析,以了解 SARS-CoV-2 的发病机制和评估治疗方法,包括中和单克隆抗体(mAbs)。然而,能够识别金黄仓鼠来源的抗原并区分特定细胞类型(如肺泡上皮细胞)的 mAbs 有限。足细胞蛋白(PDPN)是肺 I 型肺泡上皮细胞、肾脏足细胞和淋巴管内皮细胞的重要标志物。在这项研究中,使用基于细胞的免疫接种和筛选(CBIS)方法建立了针对中国仓鼠()的 PDPN 单克隆抗体 PMab-281(IgG,kappa)。还开发了 PMab-281 的去岩藻糖基化鼠 IgG 版本 281-mG-f。281-mG-f 通过流式细胞术强烈识别中国仓鼠和金黄仓鼠的 PDPN,并且可以通过免疫组织化学检测来自金黄仓鼠的肺 I 型肺泡上皮细胞、淋巴管内皮细胞和肾脏的鲍曼氏囊。这些结果表明 281-mG-f 可用于分析 SARS-CoV-2 研究中的金黄仓鼠来源的组织和细胞。

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