Abstract
Early study from our lab had shown that 70 Gy irradiated-TRAMP-C1 cells were better than freeze and thawed-cell lyses in pulsing dendritic cells (DCs) in DC-based tumor vaccine against murine prostate cancers. This study aimed to search a suitable murine prostate specific peptide for DC-based tumor vaccine and use this peptide as a model to study the influence of proteasome inhibitor on the process of DC-mediated antigen cross presentation. To achieve this goal, computer algorithms were first used to predict 4 potential peptide epitopes. Their ability to generate DC-based immunity was first screened by short term CTL and ELISPOT assay. Two of them showed promised potential as the epitopes to be presented by MHC molecules. Their ability to cause DC maturation was indicated by the increase expression of MHC-II, CD80, and CD86 molecules. Further tumor growth delay, CTL, and ELISPOT assays demonstrated that these two peptides were as efficient as irradiated TRAMP-C1 in DC-based immunotherapy for prostate cancer. This study also showed that the administration of protease inhibitor, PS-341, could not enhance the process of antigen cross presentation by DCs. I have also demonstrated the radiation could enhance the expression of ICAM-1, MHC-1, and Fas antigens by TRAMP-C1 cells. This provides an evidence to explain why the irradiated-tumor cells were better antigen sources than freeze and thawed cell lyses in DC-based immunotherapy.