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Soluble Glypican-3 Protein for Treatment of Cancer

Posted Oct 20 2010 8:00pm

Description of Invention:
Hepatocellular carcinoma (HCC) is a form of liver cancer that is among the more deadly cancers in the world. HCC is typically only detected at the later stages of cancer development, which is always associated with poor prognosis. Because HCC is often associated with liver disease, traditional chemotherapy is not an option, making surgery the most common form of treatment. As a result, there is a need for new treatments.

Glypican-3 (GPC3) is a cell surface protein that is normally involved in cell growth and differentiation. GPC3 has been shown to act through the Wnt-signaling pathway, a pathway that is often activated in a number of different cancer cell types. Significantly, the ability of GPC3 to activate signaling through Wnt requires that GPC3 be bound to the cell membrane. GPC3 is also preferentially expressed on HCC cells, suggesting it could play a particularly important role in tumorigenesis in HCC.

This invention concerns a soluble form of GPC3 that lacks its cell membrane anchoring domain. This soluble form of GPC3 maintains its ability to interact with the Wnt signaling pathway, but cannot induce the activation of the pathway because it is not bound to the cell membrane. By competing with fully functional GPC3, the soluble GPC3 is able to inhibit the growth of HCC cells, thereby decreasing the ability of tumors to grow and metastasize. This suggests that soluble GPC3 represents a possible therapeutic for HCC.

Applications:
  • Soluble GPC3 represents a potential therapeutic for patients with cancer with hyperactivated Wnt-signaling pathways
  • Specific cancers include hepatocellular cancer (HCC), melanoma, thyroid cancer, lung squamous cell carcinoma, Wilms’ tumor, neuroblastoma, hepatoblastoma, and testicular germ-cell tumors


Advantages:
  • Removal of the glycosyl-phosphatidylinositol (GPI) anchor results in a soluble form of GPC3 that can interrupt Wnt-signaling
  • Soluble GPC3 maintains the ability to compete with fully functional GPC3 despite its inability to activate signaling
  • For treatment of HCC, offers a non-invasive, potentially non-liver toxic alternative to current strategies


Development Status:
Preclinical stage of development; cell culture data with HCC cells

Inventors:
Mitchell Ho (NCI)


Patent Status:
HHS, Reference No. E-176-2010/0
US, Application No. 61/334,135 filed 12 May 2010
US, Application No. 61/350,722 filed 02 Jun 2010


Relevant Publication:
  1. Feng M, Kim H, Phung Y, Ho M. Recombinant soluble glypican 3 protein inhibits the growth of hepatocellular carcinoma in vitro. Int J Cancer. 2010 Jul 8 (E-pub ahead of print; DOI: 10.1002/ijc.25549) [ PubMed: 20617511 ]
  2. Zittermann SI, Capurro MI, Shi W, Filmus J. Soluble glypican 3 inhibits the growth of hepatocellular carcinoma in vitro and in vivo. Int J Cancer. 2010 Mar 15;126(6):1291-301. [ PubMed: 19816934 ]


Licensing Status:
Available for licensing

Collaborative Research Opportunity:
The National Cancer Institute, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information. Click here to view the NCI collaborative opportunity announcement.


Portfolios:
Cancer
Cancer - Therapeutics



For Licensing Information Please Contact:
David Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: lambertsond@mail.nih.gov
Phone: 301-435-4632
Fax: 301-402-0220


Ref No: 2176

Updated: 10/2010

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