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

Rie Kinoshita, Hiroki Sato, Akira Yamauchi, Yuta Takahashi, Yusuke Inoue, I. Wayan Sumardika, Youyi Chen, Nahoko Tomonobu, Kota Araki, Kazuhiko Shien, Shuta Tomida, Hidejiro Torigoe, Kei Namba, Eisuke Kurihara, Yusuke Ogoshi, Hitoshi Murata, Ken ichi Yamamoto, Junichiro Futami, Endy Widya Putranto, I. Made Winarsa RumaHiromasa Yamamoto, Junichi Soh, Toshihiko Hibino, Masahiro Nishibori, Eisaku Kondo, Shinichi Toyooka, Masakiyo Sakaguchi

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)569-575
Number of pages7
JournalInternational Journal of Cancer
Volume145
Issue number2
DOIs
Publication statusPublished - Jul 15 2019

Keywords

  • S100A8/A9
  • antibody
  • metastasis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Kinoshita, R., Sato, H., Yamauchi, A., Takahashi, Y., Inoue, Y., Sumardika, I. W., Chen, Y., Tomonobu, N., Araki, K., Shien, K., Tomida, S., Torigoe, H., Namba, K., Kurihara, E., Ogoshi, Y., Murata, H., Yamamoto, K. I., Futami, J., Putranto, E. W., ... Sakaguchi, M. (2019). Newly developed anti-S100A8/A9 monoclonal antibody efficiently prevents lung tropic cancer metastasis. International Journal of Cancer, 145(2), 569-575. https://doi.org/10.1002/ijc.31982