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新开发的抗 S100A8/A9 单克隆抗体能有效预防肺癌转移。

Newly developed anti-S100A8/A9 monoclonal antibody efficiently prevents lung tropic cancer metastasis.

机构信息

Department of Cell Biology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

Department of General Thoracic Surgery and Breast and Endocrinological Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

出版信息

Int J Cancer. 2019 Jul 15;145(2):569-575. doi: 10.1002/ijc.31982. Epub 2018 Dec 14.

Abstract

The metastatic dissemination of cancer cells to remote areas of the body is the most problematic aspect in cancer patients. Among cancers, melanomas are notoriously difficult to treat due to their significantly high metastatic potential even during early stages. Hence, the establishment of advanced therapeutic approaches to regulate metastasis is required to overcome the melanoma disease. An accumulating mass of evidence has indicated a critical role of extracellular S100A8/A9 in melanoma distant metastasis. Lung S100A8/A9 is induced by melanoma cells from distant organs and it attracts these cells to its enriched lung environment since melanoma cells possess several receptors that sense the S100A8/A9 ligand. We hence aimed to develop a neutralizing antibody against S100A8/A9 that would efficiently block melanoma lung metastasis. Our protocol provided us with one prominent antibody, Ab45 that efficiently suppressed not only S100A8/A9-mediated melanoma mobility but also lung tropic melanoma metastasis in a mouse model. This prompted us to make chimeric Ab45, a chimera antibody consisting of mouse Ab45-Fab and human IgG2-Fc. Chimeric Ab45 also showed significant inhibition of the lung metastasis of melanoma. From these results, we have high hopes that the newly produced antibody will become a potential biological tool to block melanoma metastasis in future clinical settings.

摘要

癌细胞向身体远处转移是癌症患者最具挑战性的问题。在所有癌症中,黑色素瘤由于其在早期阶段就具有非常高的转移潜力,因此治疗起来尤为困难。因此,需要建立先进的治疗方法来控制转移,以克服黑色素瘤疾病。大量证据表明,细胞外 S100A8/A9 在黑色素瘤远处转移中起着关键作用。来自远处器官的黑色素瘤细胞会诱导肺部的 S100A8/A9,并且由于黑色素瘤细胞具有几种能够感知 S100A8/A9 配体的受体,因此它会吸引这些细胞到富含 S100A8/A9 的肺部环境中。因此,我们旨在开发一种针对 S100A8/A9 的中和抗体,以有效阻断黑色素瘤的肺转移。我们的方案为我们提供了一种突出的抗体 Ab45,它不仅能有效抑制 S100A8/A9 介导的黑色素瘤迁移,而且能抑制小鼠模型中的肺转移黑色素瘤。这促使我们制造嵌合 Ab45,一种由小鼠 Ab45-Fab 和人 IgG2-Fc 组成的嵌合抗体。嵌合 Ab45 也显著抑制了黑色素瘤的肺转移。从这些结果来看,我们非常希望新产生的抗体将成为未来临床环境中阻断黑色素瘤转移的潜在生物工具。

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