Immunogenic Peptides and Methods of Use for Treating Prostrate and Uterine Cancers
Posted Jul 31 2007 5:00pm
Description of Invention: Cancer of the prostate is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men. Despite the use of standard therapy, including surgery, radiotherapy, chemotherapy, and/or hormonal therapy more than 30,000 men will die from prostate cancer. Moreover, current therapy has limited success against metastatic androgen insensitive prostate cancer. A potential treatment for prostate cancer is immunotherapy, either alone or in combination with standard therapies.
PAGE4 is an X chromosome-linked cancer-testis antigen that is highly expressed in prostate and uterine cancers. To this end, Drs. Jeffery Schlom, Kwong Tsang, and Ira Pastan have identified and characterized novel PAGE4 cytotoxic T-cell lymphocyte (CTL) epitopes and enhanced agonist epitopes. Preclinical studies performed by Dr. Schlom and colleagues indicate that the PAGE4 agonist epitopes bind HLA-A2 molecules at lower peptide concentrations, form more stable peptide HLA-A2 complexes, induce higher levels of production of INF-gamma, Granzyme B, TNF-alpha, IL-2, and lymphotactin by PAGE4 specific T-cell lines, and T-cell lines generated against the agonist peptide were more efficient at lysing human tumor cells expressing native PAGE4. Thus, these agonist epitopes of PAGE4 could be incorporated into immunotherapy protocols, and may constitute an alternative and/or additional approach for the treatment of PAGE4 expressing prostate and uterine cancers.
Development Status: The Laboratory of Tumor Immunology and Biology plans to initiate clinical studies utilizing this technology and collaborative opportunities may be available.
J Yokokawa et al., “Identification of cytotoxic T-lymphocyte epitope(s) and its agonist epitope(s) of a novel target for vaccine therapy (PAGE4),” Int J Cancer. 2007 Aug 1;121(3):595-605. [ PubMed abs ]
C Iavarone et al., “PAGE4 is a cytoplasmic protein that is expressed in normal prostate and in prostate cancers,” Mol Cancer Ther. 2002 Mar;1(5):329-335. [ PubMed abs ]
L Prikler et al., “Adaptive immunotherapy of the advanced prostate cancer - cancer testis antigen (CTA) as possible target antigens,” Aktuelle Urol. 2004 Aug;35(4):326-330. [article in German] [ PubMed abs ]
Licensing Status: Available for non-exclusive or exclusive licensing.
Collaborative Research Opportunity: The Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.
Portfolios: Cancer Cancer - Therapeutics Gene Based Therapies Gene Based Therapies - Therapeutics
For Additional Information Please Contact: Sabarni Chatterjee Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: chatterjeesa@mail.nih.gov Phone: 301-435-5587 Fax: 301-402-0220
Description of Invention:
Cancer of the prostate is the most commonly diagnosed cancer in men and the second leading cause of cancer death in men. Despite the use of standard therapy, including surgery, radiotherapy, chemotherapy, and/or hormonal therapy more than 30,000 men will die from prostate cancer. Moreover, current therapy has limited success against metastatic androgen insensitive prostate cancer. A potential treatment for prostate cancer is immunotherapy, either alone or in combination with standard therapies.
PAGE4 is an X chromosome-linked cancer-testis antigen that is highly expressed in prostate and uterine cancers. To this end, Drs. Jeffery Schlom, Kwong Tsang, and Ira Pastan have identified and characterized novel PAGE4 cytotoxic T-cell lymphocyte (CTL) epitopes and enhanced agonist epitopes. Preclinical studies performed by Dr. Schlom and colleagues indicate that the PAGE4 agonist epitopes bind HLA-A2 molecules at lower peptide concentrations, form more stable peptide HLA-A2 complexes, induce higher levels of production of INF-gamma, Granzyme B, TNF-alpha, IL-2, and lymphotactin by PAGE4 specific T-cell lines, and T-cell lines generated against the agonist peptide were more efficient at lysing human tumor cells expressing native PAGE4. Thus, these agonist epitopes of PAGE4 could be incorporated into immunotherapy protocols, and may constitute an alternative and/or additional approach for the treatment of PAGE4 expressing prostate and uterine cancers.
Development Status:
The Laboratory of Tumor Immunology and Biology plans to initiate clinical studies utilizing this technology and collaborative opportunities may be available.
Inventors:
Ira H Pastan (NCI)
Jeffrey Schlom (NCI)
Kwong-Yok Tsang (NCI)
Patent Status:
HHS, Reference No. E-104-2006/0
US, Application No. 12/280,534 filed 21 Feb 2007
Related Technologies:
PCT, Application No. PCT/US99/20046 filed 31 Aug 1999, Reference No. E-028-1999/0
US, Patent No. 7,399,827, Issued 15 Jul 2008, Reference No. E-028-1999/0
US, Application No. 11/704,714 filed 09 Feb 2007, Reference No. E-028-1999/0
Relevant Publication:
Licensing Status:
Available for non-exclusive or exclusive licensing.
Collaborative Research Opportunity:
The Laboratory of Tumor Immunology and Biology, Center for Cancer Research, NCI is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize this technology. Please contact John D. Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.
Portfolios:
Cancer
Cancer - Therapeutics
Gene Based Therapies
Gene Based Therapies - Therapeutics
For Additional Information Please Contact:
Sabarni Chatterjee Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: chatterjeesa@mail.nih.gov
Phone: 301-435-5587
Fax: 301-402-0220
Ref No: 1361
Updated: 08/2007