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Monoclonal Antibodies to Glypican-3 Protein and Heparin Sulfate for Treatment of Cancer

Posted Jun 14 2011 8:00pm

Description of Invention:
Hepatocellular carcinoma (HCC) is the most common form of liver cancer, and is among the more deadly cancers in the world due to its late detection and poor prognosis. HCC is often associated with liver disease, curtailing traditional chemotherapy as a treatment option. While surgical resection offers the best method for long term treatment of the disease, only a small portion of HCC patients are eligible for this procedure. As a result, there is a need for new treatments that can be successfully applied to a large population of HCC patients.

Glypican-3 (GPC3) is a cell surface protein that is preferentially expressed on HCC cells. Evidence has demonstrated that a soluble form of GPC3 that is incapable of cell signaling has the ability to inhibit the growth of HCC cells. This suggested that blocking GPC3 signaling could serve as a therapeutic approach for treating HCC.

This invention concerns monoclonal antibodies against GPC3 and their use, either by themselves or as the targeting domain for an immunotoxin, for the treatment of GPC3-expressing cancers such as HCC. Specifically, the inventors have generated two distinct monoclonal antibodies to GPC3. The first monoclonal antibody (HN3) binds to a conformational epitope on the cell surface domain of GPC3. The second monoclonal antibody (HS20) binds specifically to heparin sulfate chains on GPC3.

By blocking GPC3 function, these antibodies can inhibit the growth of HCC cells, thereby decreasing the ability of tumors to grow and metastasize. Furthermore, by using the antibodies to target a toxin to only those cells that express GPC3, cancer cells can be eliminated while allowing healthy, essential cells to remain unharmed. Thus, monoclonal antibodies to GPC3 (and corresponding immunotoxins) represent a novel therapeutic candidate for treatment of HCC, as well as other cancers associated with the differential expression of GPC3.

Applications:
  • Therapeutic candidates against cancers that overexpress GPC3
  • Antibodies for killing cancer cells by inhibiting GPC3-based cell signaling, thereby inhibiting tumor cell growth
  • Immunotoxins for killing cancer cells through the action of a toxic agent
  • Diagnostics for detecting cancers associated with GPC3 overexpression
  • Specific cancers include hepatocellular cancer (HCC), melanoma, thyroid cancer, lung squamous cell carcinoma, Wilms’ tumor, neuroblastoma, hepatoblastoma, and testicular germ-cell tumors


Advantages:
  • Monoclonal antibodies create a level of specificity that can reduce deleterious side-effects
  • Multiple treatment strategies available including the killing of cancer cells with a toxic agent or by inhibiting cell signaling
  • Non-invasive and potentially non-liver toxic alternative to current HCC treatment strategies


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

Inventors:
Mitchell Ho (NCI)


Patent Status:
HHS, Reference No. E-130-2011/0
US, Application No. 61/477,020 filed 19 Apr 2011


Relevant Publication:
  1. M Feng et al. Recombinant soluble glypican 3 protein inhibits the growth of hepatocellular carcinoma in vitro. Int J Cancer 2011 May1;128(9):2246-2247, doi 10.1002/ijc.25549. [ PMID: 20617511 ]
  2. SI Zitterman et al. Soluble glypican 3 inhibits the growth of hepatocellular carcinoma in vitro and in vivo. Int J Cancer 2010 Mar 15;126(6):1291-1301. [ PMID: 19816934 ]


Licensing Status:
Available for licensing.

Collaborative Research Opportunity:
The Center for Cancer Research, Laboratory of Molecular Biology, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize human monoclonal antibodies or immunoconjugates such as immunotoxins and antibody-drug conjugates against GPC3, soluble GPC3 and its immunoconjugates such as Fc fusion proteins, large scale antibody production, and HCC xenograft mouse models. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Cancer
Cancer - Diagnostics
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: 2271

Updated: 06/2011

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