Neutralizing antibody for S100A8/A9 soil sensing signal to prevent metastatic disease

Organotropism of cancer metastasis is driven by the ‘seed and soil’ theory where soil (metastatic microenvironment) provides signals to attract seeds (cancer cells) grow on a certain location. S100A8/A9 ‘soil sensing signal’ that binds receptors expressed many types. We aimed understand role in melanoma, breast lung cancer, develop neutralizing antibody, provide proof-of-concept for antibody inhibiting metastasis. Cell lines were obtained from ATCC. Overexpression MCAM NPTNβ was induced cDNA vector expression silenced siRNA. Recombinant protein produced in-house. Migration/invasion assays performing with Boyden Chamber method, colony formation assay agarose gel cultures, results quantitated counting crystal violet stained cells/colonies. mRNA analyzed qPCR. In mouse models, cells injected into tail vein, metastases monitored X-ray Computed Tomography metastatic foci at endpoint. A chimeric CHO-S incorporating genomic sequences heavy light chains monoclonal Fab domain human cDNA-encoded IgG2-Fc part. monocytes attracted expressing its immunosuppressed premetastatic niche. Of these receptors, highly metastatic, but not non-metastatic melanoma cells. increased migration, downregulation eliminated also resulted lost sensitivity stimulation. cells, overexpression non-metastastic which abrogated addition decoy receptor cultures. EMT-like profile anchorage independent growth, migration invasion, further ligand From antibodies, clones efficiently bound S100A8 A9 heterodimer most effectively inhibited cytokine production. The prevented models. These demonstrate cancer. metastases, suggesting pharmacological inhibition as potential option preventing disease. No conflict interest.