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