Novel synthetic antibody that limits tumor progression and metastasis.
Metastasis is the leading cause of cancer related deaths. During metastasis tumor cells degrade the basement membrane of blood vessels allowing cancer cells to enter blood vessels and spread to other tissues. Tissue invasion requires matrix metalloproteinase 14 (MMP14/MT1-MMP) which is linked to poor prognosis. More than 50 small molecule MMP inhibitors have failed in cancer clinical trials due to poor specificity and toxicity.
Queen’s researchers have identified several novel synthetic MMP14 antibodies by phage display screening using the MMP14 extracellular domain (ECD). A lead antibody (Fab 3369) inhibits MMP14 protease activity both in vitro and in metastatic cancer cells. The human IgG1 form of this antibody was effective at limiting TNBC tumor growth and metastasis in mouse models and limiting tumor progression and metastasis.
This highly selective inhibitory antibody to MMP-14 that overcomes the selectivity and toxicity issues of other small molecule inhibitors.
Researchers have identified 5 affinity matured MMP-14 antibodies with improved association/dissociation constants over the lead antibody which are currently under investigation.
MP-14 has a role in several disease states including preeclampsia, urinary bladder cancer, ovarian cancer, breast cancer, colorectal cancer, gastric cancer, epithelial skin cancers and fibrotic diseases.