Prostate Cancer Immunotherapy Development in Prostate Specific Antigen Transgenic Mice
Annual rept. 1 Sep 1999-28 Feb 2001
LOYOLA UNIV MAYWOOD IL
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Our research is focused on the development of a PSA directed immunotherapy for prostate cancer. Through repetition of the experiments with additional controls, we confirmed our conclusion of last year that PSA can serve as a tumor rejection marker in the PSA transgenic mouse in spite of the potential tolerance to the PSA protein due to its self-status. Vaccination with a PSA expressing human tumor cell line elicited a specific anti-PSA response that protected mice from a challenge of PSAOM-2 but not the control vectorOM-2 cell line. We identified PSA peptides that are immunogenic in the human HLA-A0201 haplotype. Of nine candidate peptides five have been proven to be immunogenic in the HLA-A2Dd transgenic mouse after vaccination with peptide pulsed dendritic cells. These five peptides were further characterized with binding as says to reveal that four were exclusively bound by the A2 MHC molecule and one by the murine H-2Dsup b MHC molecule. Individually, all five peptides were shown to be efficacious in inducing an anti-PSA immune response capable of protecting 33-60 of A2Dd transgenic mice challenged with the tumor cell line, PSAEL4A2Kb. The results of these experiments allow us to continue to pursue an anti-PSA directed prostate cancer immunotherapy.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research