This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by de la Luz Garcia-Hernandez, M. Articles by Kast, W. M. Search for Related Content PubMed PubMed Citation Articles by de la Luz Garcia-Hernandez, M. Articles by Kast, W. M.

Prostate Stem Cell Antigen Vaccination Induces a Long-term Protective Immune Response against Prostate Cancer in the Absence of Autoimmunity

¹ Department of Molecular Microbiology and Immunology and Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California and ² AlphaVax, Inc., Research Triangle Park, North Carolina

Requests for reprints: W. Martin Kast, University of Southern California, 1450 Biggy Street, NRT 7507, Los Angeles, CA 90033. Phone: 323-442-3870; Fax: 323-442-4433; E-mail: mkast{at}usc.edu.

Key Words: prostate cancer • vaccination • PSCA • cancer vaccines • animal/transgenic models for tumor immunobiology • genitourinary cancers: prostate

Prostate stem cell antigen (PSCA) is an attractive antigen to target using therapeutic vaccines because of its overexpression in prostate cancer, especially in metastatic tissues, and its limited expression in other organs. Our studies offer the first evidence that a PSCA-based vaccine can induce long-term protection against prostate cancer development in prostate cancer–prone transgenic adenocarcinoma mouse prostate (TRAMP) mice. Eight-week-old TRAMP mice displaying prostate intraepithelial neoplasia were vaccinated with a heterologous prime/boost strategy consisting of gene gun–delivered PSCA-cDNA followed by Venezuelan equine encephalitis virus replicons encoding PSCA. Our results show the induction of an immune response against a newly defined PSCA epitope that is mediated primarily by CD8 T cells. The prostates of PSCA-vaccinated mice were infiltrated by CD4-positive, CD8-positive, CD11b-positive, and CD11c-positive cells. Vaccination induced MHC class I expression and cytokine production [IFN-, tumor necrosis factor-, interleukin 2 (IL-2), IL-4, and IL-5] within prostate tumors. This tumor microenvironment correlated with low Gleason scores and weak PSCA staining on tumor cells present in hyperplastic zones and in areas that contained focal and well-differentiated adenocarcinomas. PSCA-vaccinated TRAMP mice had a 90% survival rate at 12 months of age. In contrast, all control mice had succumbed to prostate cancer or had heavy tumor loads. Crucially, this long-term protective immune response was not associated with any measurable induction of autoimmunity. The possibility of inducing long-term protection against prostate cancer by vaccination at the earliest signs of its development has the potential to cause a dramatic paradigm shift in the treatment of this disease. [Cancer Res 2008;68(3):861–9]

This article has been cited by other articles:

				C. Mennuni, S. Ugel, F. Mori, B. Cipriani, M. Iezzi, T. Pannellini, D. Lazzaro, G. Ciliberto, N. La Monica, P. Zanovello, et al. Preventive Vaccination with Telomerase Controls Tumor Growth in Genetically Engineered and Carcinogen-Induced Mouse Models of Cancer Cancer Res., December 1, 2008; 68(23): 9865 - 9874. [Abstract] [Full Text] [PDF]

				M. A. de Witte, G. M. Bendle, M. D. van den Boom, M. Coccoris, T. D. Schell, S. S. Tevethia, H. van Tinteren, E. M. Mesman, J.-Y. Song, and T. N. M. Schumacher TCR Gene Therapy of Spontaneous Prostate Carcinoma Requires In Vivo T Cell Activation J. Immunol., August 15, 2008; 181(4): 2563 - 2571. [Abstract] [Full Text] [PDF]

				O. J. Finn Cancer Immunology N. Engl. J. Med., June 19, 2008; 358(25): 2704 - 2715. [Full Text] [PDF]