Recombinant Anti-mesothelin Immunotoxin SS1P (anti-mesothelin dsFv-PE38) as a Therapeutic Agent and Diagnostic Tool for Multiple Cancer Types

Background:
The National Cancer Institute's Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop or commercialize the anti-mesothelin immunotoxin SS1P as an anti-tumor agent. Additionally, it can be used for the detection of mesothelin-expressing cells present in a biological sample. The technology is also available for exclusive and non-exclusive licensing.

Technology:
Mesothelin is a glycoprotein, whose expression has been largely restricted to mesothelial cells in normal tissues. Mesothelin has been shown to be expressed in several cancers including mesothelioma, lung cancer, pancreatic cancers, gastric cancers and ovarian cancers, and has the potential of being used as a novel target for the development of new treatments. The SS1P immunotoxin is a recombinant immunotoxin generated by the fusion of a high affinity anti-mesothelin Fv (SS1) with a 38 kDa portion of Pseudomonas Exotoxin A (PE38). SS1P can be used to kill cells expressing mesothelin on their surfaces, such as mesothelioma, ovarian cancer, lung cancer, pancreatic cancer and stomach cancer.

Value Proposition:

• SS1P immunotoxin is available for use as a therapy for mesothelin-expressing cancers;
• Successful clinical testing has been done for the treatment of mesothelioma and ovarian cancer with low side effects
• Can be used as a stand alone treatment and in combination chemotherapy.

R&D Status:

• Phase 1 studies have been completed for mesothelin-expressing cancers such as mesothelioma, ovarian cancer and pancreatic cancer.
• Animal studies: The combination of Taxol and SS1P exerts a synergistic antitumor effect in immunodeficient mice implanted with A431/K5 tumors expressing mesothelin, but not in cell culture. This effect is not secondary to increased tumor uptake of the immunotoxin. Synergy could be due to improved immunotoxin distribution within the tumor or could involve factors released by other cell types in the tumors..

Further R&D Needed:
Phase 2 clinical trials of SS1P using SS1P and standard chemotherapy are being planned for malignant mesothelioma and other mesothelin-expressing malignancies.

Patent Status:

• U.S. Patents: 7,081,518; 4,892,827; 6,051,405; 5,863,745; 5,696,237; 5,747,654; 6,147,203; 6,558,672; 6,153,430; 6,083,502.
• U.S. Patent Applications: 09/684,599; 09/581,345; 60/681,104
• PCT Applications: PCT/US01/18503 and PCT/US2006/018502

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

Reference:  #581 LW

Posted 11/21/2007