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

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.

Keywords: S100A8/A9; antibody; metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Neutralizing / administration & dosage
  • Antibodies, Neutralizing / pharmacology
  • Calgranulin A / immunology
  • Calgranulin B / immunology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / secondary*
  • Melanoma / drug therapy*
  • Melanoma / metabolism
  • Mice
  • Treatment Outcome
  • Tumor Microenvironment / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Calgranulin A
  • Calgranulin B
  • S100A8 protein, human
  • S100A9 protein, human