Identification and characterization of novel PAGE4 cytotoxic T-cell lymphocyte (CTL) epitopes and enhanced agonist epitopes.

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.

Publications which may provide background information for this technology include:

1. 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]
2. 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]
3. 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]  [

Preclinical

U.S. Provisional Application No. 60/776,506 filed 24 Feb 2006 (HHS Reference No. E-104-2006/0-US-01)

PCT Application No. PCT/US2007/004603 filed 21 Feb 2007, which published asWO 2007/100607 on 07 Sep 2007 (HHS Reference No. E-104-2006/0-PCT-02)

Inventors:
Jeffrey Schlom, Kwong-Yok Tsang, Ira Pastan (NCI)

Licensees Sought:
Available for non-exclusive or exclusive licensing.

Collaborative Research Opportunity:
The NCI Laboratory of Tumor Immunobiology is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize cancer vaccine technology encompassing PAGE4. Please contact Patrick Twomey, Ph.D., in the NCI Technology Transfer Center at twomeyp@mail.nih.gov and/or 301/496-0477 for more information.