Anti-Angiogenic Properties of Type 1 Repeats of Thrombospondin 1 (TSP repeat) (BIDMC 402)

Category:    Drug Discovery Tools

KeyWords:  Cancer;  Inflammation;  Angiogenesis;  

BIDMC ID:    402

Abstract:

Tumors attract blood vessels through a process called angiogenesis. The balance between inhibitors and stimulators plays a vital role in the initiation of angiogenesis. The ingrowth of new capillary into developing tumors is essential for tumor progression. Thrombospondin 1(TSP-1) is a potent inhibitor of angiogenesis. It is a calcium binding glycoprotein that modulates endothelial cell growth, cell attachment, migration and proliferation. The major form of thrombospondin secreted by platelets and endothelial cells is TSP-1. The thrombospondin type 1 repeats have been shown to inhibit angiogenesis. Conversely, other domains of thrombospondin have been shown to promote endothelial growth. This technology describes the use of a recombinant version of the second type 1 repeat of TSP-1 to inhibit tumor growth. This recombinant construct has been designed to include all of the sequences of TSP-1 that have anti-tumor activity. This protein has been shown to be a potent inhibitor of experimental tumor growth in mice. Antiangiogenic therapy has little toxicity, does not require the therapeutic agent to enter tumor cells or cross the blood brain barrier, and does not induce drug resistance. Thus, the development of pharmaceuticals that inhibit angiogenesis is an important therapeutic goal. Angiogenesis represents an emerging therapeutic target, which by 2006, is expected to command a market of $1.75 billion.

Inventor:   Dr. John W. Lawler

Commercial Opportunity:

The TSP repeat molecules are drug candidates for treatment of cancer, psoriasis, diabetic retinopathy,arthritis and any disease state where angiogenesis plays a role.

Competitive Advantages:

The recombinant proteins covered in this patent application have been engineered to include only the anti-tumor activities of native thrombospondin. They are stable in circulation and are effective in treating multiple different types of tumors. Also, because they arederived from naturally occurring proteins they are less likely to display toxic side effects.

Related Publications:

Am J Pathol. 2004 Aug;165(2):541-52.
Expression of the type-1 repeats of thrombospondin-1 inhibits tumor growth through activation of transforming growth factor-beta.

http://ajp.amjpathol.org/cgi/content/full/165/2/541?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=Lawler, J&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT

Int J Biochem Cell Biol. 2004 Jun;36(6):1038-45
Tumor progression: the effects of thrombospondin-1 and -2.
Lawler J, Detmar M.

http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCH-4BYBYC9-1&_coverDate=06/30/2004&_alid=219471878&_rdoc=1&_fmt=&_orig=search&_qd=1&_cdi=5171&_sort=d&view=c&_acct=C000053982&_version=1&_urlVersion=0&_userid=1625289&md5=78b9a1c18fbbf9c8d994f0e7e9678439

State of Development:

Medical Center seeks commercial partner to further develop these molecules as therapeutics.

Related Technology URL:

http://research.bidmc.harvard.edu/research/ResearchPIInfo.ASP?Submit=Display&PersonID=958

Patent Status:

US Patent and foreign patent coverage.
      Published PCT applications available:
      TSP repeat: PCT/US01/17250

TVO Contact Info:
     Jason S Felsch
     Senior Licensing Manager, TVO
     jfelsch@bidmc.harvard.edu
     Phone: 617-667-9490   Fax: 617-667-0646

     Beth Israel Deaconess Medical Center
     Technology Ventures Office  Room: BR-202
     330 Brookline Avenue
     Boston, MA 02215