A viral vaccine expressing these 3 costimulatory molecules (TRICOM) was generated and used in combination with Sotrastaurin ic50 recombinant virus expressing carcinoembryonic antigen to treat carcinoembryonic antigen-expressing tumors with good results. Arlen and colleagues27 performed a phase I study using TRICOM with rV-PSA and rF-PSA in 15 patients with metastatic HRPC. The study examined 5 different regimens with 3 patients in each arm: all received rF-PSA/TRICOM,

4 arms (arms 2 through Inhibitors,research,lifescience,medical 5) received prime rVPSA/TRICOM followed by 3 boosts with rF-PSA/TRICOM, 2 arms (arms 4 and 5) received a rF-GM-CSF vaccine in addition, and 1 arm (arm 3) received recombinant GM-CSF protein as an adjuvant. Overall, 9 of 15 patients had decreased PSA velocity after vaccination. Median time to clinical progression was 20.5 weeks. Large, prospective, randomized

trials using this regimen with GM-CSF are ongoing. Others have examined DNA vaccines with PSA to induce an immune response. DNA vaccines have the advantage of ease of production and administration, as well as lack of viral Inhibitors,research,lifescience,medical antigens that may generate an immune response. The disadvantage is that the rate of cell transfection is low; thus the ability to produce an immune response is weakened. In a phase I dose-escalation trial on 9 patients with HRPC, varying doses (100, 300, and 900 µg) of a DNA plasmid engineered to Inhibitors,research,lifescience,medical express PSA were administered to men 5 times at 4-week intervals along with GM-CSF and IL-2 around the time of vaccine administration.28 The treatment was well tolerated, and T-cell and IgG antibody production were robust. Three patients Inhibitors,research,lifescience,medical had decreased PSA levels after treatment. Preliminary studies for a number of other immunotherapies based on viral and DNA vaccines have been performed, including PSMA as a target in both DNA and viral Inhibitors,research,lifescience,medical vaccines,29 IL-2 delivery as a transgene in viral vaccines,30

and others. Ongoing research will assist in determining the best targets, vectors, immunization strategies, and adjuvants to mature this area of potential prostate cancer therapy. Dendritic Cell Therapy Dendritic cells are APCs present in nearly all tissues. Dendritic cells present antigens through others their MHC class 1 and 2 receptors and thus can induce immune responses by activating both CD8 and CD4 T cells to develop a potent antitumor response. Autologous dendritic cells can be grown in vitro and transfected with antigen, cytokines, or other agents before reintroduction to the patient to direct an immune response. Numerous experimental immunologic regimens have adopted dendritic cells as the basis of their protocol. Sipuleucel-T (APC8015; Dendreon, Seattle, WA) is one of the most extensively studied dendritic cell modalities. It consists of autologous dendritic cells, which are harvested by leukophoresis. The cells are loaded by coculture with PA2024, a recombinant fusion protein of PAP and GM-CSF. PAP is an enzyme localized to the prostate and expressed in 95% of all prostate cancers.