Monoclonal Antibody 1G6-D7 Blocks Cancer Metastasis
Patent Number: PCT/US15/059104; US 14/932,908
Executive Summary:
General Description:
USC scientists recently developed a monoclonal antibody, called 1G6-D7, which targets tumor-secreted Hsp90a. 1G6-D7 binds the active site of tumor-secreted Hsp90a and inhibits both de novo tumor formation and expansion of pre-formed tumors in mice. This development suggests an alternative therapeutic approach to target Hsp90 in cancer, i.e. selective inhibition of the tumor-secreted Hsp90a, instead of the intracellular Hsp90a and Hsp90b that have been proven toxic.
Strengths:
Weaknesses:
Patent Status: Pending
Publications:
“Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression.” Oncogene, October 10 2016.
Inventor Bio: Wei Li
http://keck.usc.edu/faculty/wei-li/
Executive Summary:
- Invention Type: Therapeutic
- Patent Status: Pending
- Patent Link: http://usc.flintbox.com/public/filedownload/9787/NCD%202014-219%20-%20Monoclonal%20Antibody%201G6-D7%20Blocks%20Cancer%20Metastasis.pdf
- Research Institute: University of Southern California
- Disease Focus: Cancer, including triple negative breast cancer
- Basis of Invention: Both intracellular and extracellular heat shock protein-90 (Hsp90) family proteins (a and b) have been shown to support tumor progression. Targeting intracellular Hsp90, however, has proven too toxic to cancer patients resulting in a very small number of trials advancing to receive regulatory approval for human treatment to date. The role of extracellular Hsp90 in cancer recently has been unveiled by USC scientists who showed that secreted Hsp90α is essential for tumor formation, invasion, and metastasis of triple negative breast cancer. In contrast to normal cells, which do not secrete Hsp90-α under physiological conditions, more than 50% of all invasive, HIF-1-positive tumors in humans constitutively secrete Hsp90-α. Furthermore, targeting the secreted form of Hsp90 does not affect normal tissue functions. Therefore, selective inhibition of tumor-secreted Hsp90a, which is nonessential for normal cells, could be an effective therapeutic approach for certain cancers.
- How it works: Monoclonal antibody, called 1G6-D7, binds the active site of tumor-secreted Hsp90a and inhibits both de novo tumor formation and expansion of pre-formed tumors in mice. This development suggests an alternative therapeutic approach to target Hsp90 in cancer, i.e. selective inhibition of the tumor-secreted Hsp90a, instead of the intracellular Hsp90a and Hsp90b that have been proven toxic
- Lead Challenge Inventor: Wei Li
- Development Stage: Pre-clinical – tested in vitro and in vivo
- Clinical Applications:
- Treatment and prevention of tumor formation and metastasis
- Research reagent (monoclonal antibody)
- Treatment and prevention of tumor formation and metastasis
General Description:
USC scientists recently developed a monoclonal antibody, called 1G6-D7, which targets tumor-secreted Hsp90a. 1G6-D7 binds the active site of tumor-secreted Hsp90a and inhibits both de novo tumor formation and expansion of pre-formed tumors in mice. This development suggests an alternative therapeutic approach to target Hsp90 in cancer, i.e. selective inhibition of the tumor-secreted Hsp90a, instead of the intracellular Hsp90a and Hsp90b that have been proven toxic.
Strengths:
- An alternative therapeutic approach to target Hsp90 in cancer by targeting tumor-secreted Hsp90α
- 1G6-D7 Mab shown to inhibit new tumor formation, growth of existing tumors, and metastasis in mouse CDX models
- Potential to treat multiple types of cancer, including but not limited to breast and lung cancer
- More specific to tumor than normal cells
Weaknesses:
- Many HSP90 inhibitors on market but most have high toxicity
Patent Status: Pending
Publications:
“Evolutionarily conserved dual lysine motif determines the non-chaperone function of secreted Hsp90alpha in tumour progression.” Oncogene, October 10 2016.
Inventor Bio: Wei Li
http://keck.usc.edu/faculty/wei-li/