Development of STEAP-Based Vaccines for the Treatment of Prostate Cancer
Annual summary rept. 1 Nov 2004-31 Oct 2005
CALIFORNIA UNIV LOS ANGELES
Pagination or Media Count:
Six-Transmembrane Epithelial Antigen of the Prostate STEAP has been considered an attractive target, because it is overexpressed in human prostate cancer tissues. Recently two hSTEAP peptides have been selected for their capacity to bind and stabilize HLA-A0201 molecules. In addition peptide-specific human CTL cell lines recognized hSTEAP-expressing cells, lysing them. These findings suggest that STEAP is a promising antigen for tumor immunotherapy. In this study we determined the effectiveness of STEAP-based vaccination in prophylactic and therapeutic mice models by using two delivery systems and three vaccination schemes. In the first vaccination scheme, mice were primed and boosted with an expression vector that contains mSTEAP cDNA by gene gun. In the second one, mice were primed with mSTEAP cDNA by gene gun and boosted with Venezuelan Encephalitis Virus Replicons VRP encoding mSTEAP and in the last vaccination scheme mice where primed and boosted with mSTEAP-VRP. Our results show that mSTEAP-based vaccination, no matter the scheme of treatment, significantly delays tumor growth. The prime-boost vaccination scheme was able to induce a specific CD8 T cell response responsible for tumor eradication in complete absence of autoimmunity development but was unable to control preestablish.
- Medicine and Medical Research