Memorial Sloan Kettering Cancer Center

Beijing University of Technology

Ludwig Institute for Cancer Research Limited

Olivia Newton-John Cancer Research Institute

Monash University

Peter W Janes

Dimitar B Nikolov

Martin Lackmann

Nayanendu Saha

Lakmali Atapattu Mudiyanselage

Andrew Ewart Scott

Andrew Mark Scott

Andrew M Scott

DB Memorial Sloan Kettering Cancer Ctr Nikolov

Expression of proteolytically active, high molecular weight ADAM10 protease is relatively increased in tumour cells that also express the putative tumour stem cell marker CD133. A recombinant humanized antibody or antibody fragment based on 8C7 monoclonal antibody may be used to selectively bind to proteolytically active, high molecular weight ADAM10 protease to thereby detect tumour cells and also as a therapeutic agent for treating cancers, tumours and other malignancies inclusive of leukemia, lymphoma, lung cancer, colon cancer, adenoma, neuroblastoma, brain tumour, renal tumour, prostate cancer, sarcoma and/or melanoma.

Anti-metalloprotease antibody for diagnosis and treatment of cancers

Expression of proteolytically active, high molecular weight ADAM protease is relatively increased in tumor cells that also express the putative tumor stem cell marker CD133. An antibody or antibody fragment such as 8C7 monoclonal antibody may be used to selectively bind to proteolytically active, high molecular weight ADAM10 protease to thereby detect tumor cells and also as a therapeutic agent for treating cancers, tumors and other malignancies inclusive of leukemia, lymphoma, lung cancer, colon cancer, adenoma, neuroblastoma, brain tumor, renal tumor, prostate cancer, sarcoma and/or melanoma.

Elucidation of the crystal structure of an ADAM10 substrate-recognition and proteinase-positioning module comprising the protein cysteine-rich and disintegrin domains, and detailed functional analysis revealed that an acidic pocket within the cysteine-rich domain forms a substrate-recognition site. The binding of this pocket to receptor/ligand complexes facilitates effective ligand cleavage, which is prevented when critical residues within the pocket are changed. This provides use of the surface pocket within the extracellular domain of ADAM10, and the corresponding structure in related proteases such as ADAM17, as a target for structure-based computational and high-throughput screens for small-molecule substrate-specific inhibitors or monoclonal antibodies that inhibit ADAM protease cleavage of ephrins and other ADAM10 or ADAM17 substrates. These inhibitors will be useful in therapeutic intervention of tumour development, invasion and metastasis and other diseases which involve the activity of the ADAM10 and ADAM17 proteases, such as inflammation, cardio-vascular disease, arthritis and other auto-immune diseases.

Antibody against a human ADAM protease

Growing community of inventors

Hawthorn East, Australia

Peter W Janes