Prostate cancer is the second leading cause of mortality from cancer among men in the US. The development of strategies for control of prostate cancer is essential for public health. Prostate-specific antigen (PSA) is a likely target for immunotherapy, and research has indicated the important role of dendritic cells in eliciting effective immune response. In this application, for expression of PSA, Medigen's new TC83 vector will be used that is associated with targeting lymphoid tissue and dendritic cells in vivo (Pushko, 2005). Further, we propose the rational design and optimization of PSA in order to enhance its immunogenic/therapeutic characteristics. The TC83 vector will be configured to express in vivo the following antigens: (1) soluble PSA (sPSA);(2) oligomeric PSA (oligoPSA);and (3) membrane-bound PSA (tmPSA). Vector virus-like particles (vVLPs) for expression of sPSA, oligoPSA, or tmPSA gene will be generated and administered to experimental PSA tg mice to express genes in vivo, thus eliciting immune responses to synthetic PSA. The hypothesis is that the use of TC-83 vector and the rational design of PSA will increase immunogenicity in vivo up to 10,000 times through additional pathways including targeting of dendritic and cross-presentation. Immunogenicity, safety, and feasibility of synthetic vaccines will be evaluated.
