Use of a novel camelid-inspired human antibody demonstrates the importance of MMP-14 to cancer stem cell function in the metastatic process.

摘要: Matrix metalloproteinases (MMPs) are considered excellent targets for cancer therapy because of their important roles in multiple aspects tumor growth and metastatic spread. However, not all MMPs, or even activities specific promote cancer. Therefore, there is a need highly inhibitors. Monoclonal antibodies provide the potential degree specificity required, but isolation able to inhibit protease with high selectivity challenging. Proteolysis lies recognition substrate around active site, which generally forms concave cleft inaccessible by human IgGs. Inspired camelid antibodies, have convex paratopes, we produced recombinant IgG, designated 3A2, binds MMP-14, inhibiting its activity, activity homologous MMPs. In 4T1 metastatic, syngeneic, orthotopic model breast cancer, IgG 3A2 markedly inhibited primary tumor, more importantly reduced spread lungs liver 94%. Stem cells population expressed twice as much MMP-14 mRNA bulk cells. addition reducing dissemination stem cells, would be expected from inhibition MMP-14's ability degrade components extracellular matrix, also individual proliferate produce colonies. We conclude that it possible sufficient development therapeutics has therapeutic potential.