A Novel Recombinant Immunotoxin SS1P (anti-mesothelin dsFv-PE38): A Therapeutic Treatment for Lung Cancer and Other Mesothelin Expressing Cancers
Description of Invention:
Mesothelin is a cell surface glycoprotein whose expression is largely restricted to mesothelial cells in normal tissues. Significantly, mesothelin is also highly expressed in many cancers (including malignant mesothelioma, ovarian cancer, lung cancer, pancreatic carcinomas, gastric carcinomas, etc.). As a result, mesothelin is an excellent target for immunotherapy.
NIH inventors have generated high affinity antibodies to mesothelin (SS1) and fused them to various functional fragments of Pseudomonas Exotoxin A (PE) to produce the immunotoxin SSIP. New SS1P constructs include PE fragments and mutants with reduced immunogenicity, resulting in immunotoxins with greater efficacy. SS1P activity was previously shown in patients suffering from mesothelioma and ovarian cancer; laboratory studies now demonstrate cytotoxicity against lung carcinoma cells. Additionally, SS1P has shown synergy with front line cancer therapeutics in a mouse model, making SS1P an excellent candidate both a stand-alone therapeutic and a combination therapeutic.
Applications:
SS1P can be used as a therapy for mesothelin expressing cancers, including mesothelioma, ovarian cancer and lung adenocarcinoma
The immunotoxin can be used in combination with standard chemotherapy
Advantages:
Immunotoxins are highly selective for cancer cells, reducing side-effects due to the non-specific killing of normal cells
Strong synergy has been shown between SS1P and standard front line cancer therapies in the treatment on lung adenocarcinoma
Less immunogenic PE variants increase the efficacy of the immunotoxin
Patent Status:
DHHS Reference No. E-139-1999/0 --
U.S. Patent No. 7,081,518 issued 25 Jul 2006, entitled “Anti-Mesothelin Antibodies Having High Binding Affinity”
Related Technologies:
U.S. Patents 6,051,405, 5,863,745, and 5,696,237 entitled "Recombinant Antibody-Toxin Fusion Protein" [HHS Ref. No. E-135-1989/0];
U.S. Patents 5,747,654, 6,147,203, and 6,558,672 entitled "Recombinant Disulfide-Stabilized Polypeptide Fragments Having Binding Specificity" [HHS Ref. No. E-163-1993/0];
U.S. Patent 6,153,430 and U.S. Patent Application 09/684,599 entitled "Nucleic Acid Encoding Mesothelin, a Differentiation Antigen Present on Mesothelium, Mesotheliomas and Ovarian Cancers" [HHS Ref. No. E-002-1996/0];
U.S. Patent 6,083,502 entitled "Mesothelium Antigen and Methods and Kits for Targeting It" [HHS Ref. No. E-002-1996/1];
U.S. Patent Application 09/581,345 entitled "Antibodies, Including Fv Molecules, and Immunoconjugates Having High Binding Affinity for Mesothelin and Methods for Their Use" [HHS Ref. No. E-021-1998/0];
U.S. Patent Application 10/297,337 entitled "Pegylation of Linkers Improves Antitumor Activity and Reduces Toxicity of Immunoconjugates" [HHS Ref. No. E-216-2000/2];
U.S. Patent Application 11/920,222, entitled "Anti-Mesothelin Antibodies Useful For Immunological Assays" [HHS Ref. No. E-015-2005/0-US-01];
U.S. Patent Application 11/997,202 entitled "Mutated Pseudomonas Exotoxins with Reduced Antigenicity" [HHS Ref. No. E-262-2005/0]; and
U.S. Patent Application 60/969,929 entitled "Deletions in Domain II of Pseudomonas Exotoxin A that Remove Immunogenic Epitopes without Affecting Cytotoxic Activity" [HHS Ref. No. E-292-2007/0]
Licensing Status: The technology is available for exclusive and non-exclusive licensing.
Collaborative Research Opportunity:
The National Cancer Institute Laboratory of Molecular Biology is seeking statements of capability or interest from parties interested in collaborative research to further develop immunotoxin SS1P. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.
Portfolios: Cancer
Cancer -Diagnostics-In Vitro-MAb Based Cancer -Diagnostics-In Vivo-Conjugate Chemistry Cancer -Therapeutics-Immunoconjugates-Mab Cancer -Therapeutics-Immunoconjugates-Toxins Cancer -Diagnostics Cancer -Therapeutics
For Additional Information Please Contact: David A. Lambertson Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd, Suite 325
Rockville, MD 20852-3804
Phone: (301)435-4632
Email: lambertsond@mail.nih.gov
Fax: (301) 402-0220
