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

• Published in: International journal of cancer 2019-07, Vol.145 (2), p.569-575
• Main Authors: Kinoshita, Rie, Sato, Hiroki, Yamauchi, Akira, Takahashi, Yuta, Inoue, Yusuke, Sumardika, I Wayan, Chen, Youyi, Tomonobu, Nahoko, Araki, Kota, Shien, Kazuhiko, Tomida, Shuta, Torigoe, Hidejiro, Namba, Kei, Kurihara, Eisuke, Ogoshi, Yusuke, Murata, Hitoshi, Yamamoto, Ken‐ichi, Futami, Junichiro, Putranto, Endy Widya, Ruma, I Made Winarsa, Yamamoto, Hiromasa, Soh, Junichi, Hibino, Toshihiko, Nishibori, Masahiro, Kondo, Eisaku, Toyooka, Shinichi, Sakaguchi, Masakiyo
• Format: Article
• Language: English
• Subjects: antibody; Cancer; Immunoglobulin G; Lung cancer; Medical research; Melanoma; Metastases; Metastasis; Monoclonal antibodies; Organs; S100A8/A9
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.31982

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. What's new? A new antibody could help stop lung metastasis of melanoma. The S100A8/A9 heterodimer mediates the establishment of lung metastases, and in this paper, the authors set out to develop a neutralizing antibody against it. The antibody they came up with, Ab45, inhibits melanoma mobility and lung metastasis in a mouse model. They then created a chimera of mouse Ab45‐Fab and human IgG2‐Fc. This chimeric Ab45 also successfully thwarted lung metastases, suggesting the new antibody may find a role in human treatments.