Novel Cancer Treatment Methods Using Angiogenesis Inhibitors

Background:
The National Cancer Institute's Cell and Cancer Biology Branch, Laboratory of Extracellular Matrix Pathology is seeking statements of capability or interest from parties interested in collaborative research and/or partnership agreements to further develop and commercialize novel adjuvant therapies. The technology is also available for exclusive or non-exclusive licensing.

Matrix metalloproteinases (MMPs) are a member of a group of enzymes that can break down proteins normally found in the spaces between cells and tissues. Although MMPs are essential for numerous cellular processes, excessive MMP activity can promote angiogenesis and metastasis by helping cells spread and set up a new blood supply to support tumor growth. Although protein tissue inhibitor of metalloproteinases (TIMPS) are capable of inhibiting almost every member of the MMP family, human protein tissue inhibitor of metalloproteinases-2 (TIMP-2) has been shown to inhibit angiogenesis in vivo independent of metalloproteinase inhibition.

Technology:
Inventors at NCI have demonstrated that TIMP-2, as well as TIMP-2 variants that lack metalloproteinase inhibitor activity can revert aggressive tumor cell phenotype to a more differentiated state. In addition, TIMP-2 has the ability to enhance the efficacy of cytotoxic drugs by sensitizing tumor cells to the induction of apoptosis. This invention involves the disclosure of novel methods of cancer therapy using TIMP-2 that combine known angiogenesis inhibition with newly discovered direct tumor-differentiating and chemo-sensitizing activity. This type of adjuvant therapy has application in the treatment of wide variety of carcinomas and melanomas.

R&D Status:
In vivo and in vitro experiments have been conducted, with on-going development.

IP Status:
U.S. Provisional Application No. 60/953,352 filed 01 Aug 2007

Value Proposition:

• A novel cancer therapy that combines the known anti-angiogenic activity of TIMP-2 with novel direct tumor-differentiating and chemo-sensitizing activity of TIMP-2.
• Ability to use TIMP-2 or TIMP-2 variants to inhibit tumor cell growth, promote tumor cell differentiation, and enhance cytotoxic activity of a chemotherapeutic agent.
• Potential to treat a wide variety of carcinomas and melanomas.

Further R&D Needed:

• Determine effects of TIMP-2 recombinant protein, mutants, peptides, and gene therapy in additional in vivo models using xenografts in nude mice and syngeneic orthotopic murine tumor models.
• Completion of a high throughput TIMP-2/alpha3 beta1 integrin screening assay for identification of lead compounds for the development of small molecule analogs that mimic tumor-differentiation and chemo-sensitization activity of TIMP-2 and TIMP-2 mutants devoid of metalloproteinase inhibitory activity.

Contact Information:
John D. Hewes, Ph.D., NCI Technology Transfer Center
Phone: 301-435-3121
E-mail: Hewesj@mail.nih.gov

Reference:  #631 AC

Posted 03/20/2008