Background

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.

Technology Overview

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. Affinity maturation of anti-MMP-14 antibodies is currently underway.

Publication Links

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5601659/

Frontiers | Immune Infiltration of MMP14 in Pan Cancer and Its Prognostic Effect on Tumors | Oncology (frontiersin.org)

Benefits

This highly selective inhibitory antibody to MMP-14 overcomes the selectivity and toxicity issues of other small molecule inhibitors.

Applications

MMP-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.

MMP-14 Antibodies as Novel Therapeutics for Metastatic Cancers

Patents

IP Status

Seeking