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Kansas State University

Research Foundation
Kansas State University
2005 Research Park Circle
Suite 105
Manhattan, KS 66502-5020
Tel: 785-532-5720
Fax: 785-532-3920
tech.transfer@k-state.edu

An Urokinase Cleaveage Sequence-Modified Porin for the Selective Treatment of Various Cancers

Reference Number: 07-28

Inventors: Stephan H. Bossmann; Deryl L. Troyer; Michael Niederweis; Matthew T. Basel

Background:

In 2006, there were an estimated 1.4 million cases of cancer in the United States. Researchers are on the hunt for ways to fight this disease and lower the number of people that die from it. In the fight against cancer, researchers are always trying to discover agents that will distinguish cancer cells from normal cells and are cytotoxic to the cancer cells. MspA, a porin isolated from Mycobacterium smegmatis, shows promise on both fronts.

This invention is a new peptide comprised of MspA and a urokinase cleavage sequence. This process increases the sensitivity of the treatment of cancer cells that over-express urokinase rather than killing the normal bystander-cells. The increased toxicity of MspA over compounds currently on the market makes it a better option to combat the cancer cells. Cancer treatment with MspA requires much less protein than other proteins designed for cancer treatment and can treat virtually all cancer cells that over-express urokinase.

Advantages:

Advantages of this IP over previous methods:

  • MspA is 1000 times more toxic to cancer cells than, for instance, the well-known “hecate” oligopeptide
  • Can activate the cation-selective channel of MspA by enzymatic activation in the interstitium in close proximity of the cell-membranes of the cancer cells
  • MspA can reconstitute from the outside in the cancer cells’ outer membranes
  • MspA can act fast, because it does not have to undergo the process of endocytosis
  • Protein-modified MspA acts as a “prodrug” and becomes activated by urokinase
  • MspA will most likely be able to activate T-cells
  • Cancer treatment with MspA requires far less protein than other proteins designed for the treatment of cancer
  • MspA can treat virtually all cancer cells that over-express urokinase
  • Protein-modified MspA can be given in higher, relative, doses compared to other protein drugs against cancer

Applications

This innovative technology can be used to:

  • Treatment of all cancer cells that over-express urokinase, e.g. all forms of metastasing cancer.
  • MspA can be delivered in (thermophilic) stealth (PEGylated) liposomes possessing antibodies, steroids, folic acid or other (macro)molecules to solid tumors
    • The combination with urokinase-activation further enhances the specificity of the delivery system
  • MspA can be used as assay to detect the presence of urokinase

Patent Status

  • Provisional patent application filed in March 2008.

Kansas State University Research Foundation seeks to have discussions with companies that are interested in licensing and/or research collaborations.

Interested parties should contact:

National Institute for Strategic Technology Acquisition and Commercialization (NISTAC)
2005 Research Park Circle Manhattan, KS 66502
Tel: 785-532-3900 Fax: 785-532-3909
E-Mail: nistac@ksu.edu