A novel alphavirus vaccine encoding prostate-specific membrane antigen elicits potent cellular and humoral immune responses.

PURPOSE: Prostate-specific membrane antigen (PSMA) is an attractive target for active immunotherapy. Alphavirus vaccines have shown promise in eliciting immunity to tumor antigens. This study investigated the immunogenicity of alphavirus vaccine replicon particles (VRP) that encode PSMA (PSMA-VRP). EXPERIMENTAL DESIGN: Cells were infected with PSMA-VRP and evaluated for PSMA expression and folate hydrolase activity. Mice were immunized s.c. with PSMA-VRP or purified PSMA protein. Sera, splenocytes, and purified T cells were evaluated for the magnitude, durability, and epitope specificity of the anti-PSMA response. Antibodies were measured by flow cytometry, and cellular responses were measured by IFN-gamma enzyme-linked immunospot and chromium release assays. Cellular responses in BALB/c and C57BL/6 mice were mapped using overlapping 15-mer PSMA peptides. A Good Laboratory Practice-compliant toxicology study was conducted in rabbits. RESULTS: PSMA-VRP directed high-level expression of active PSMA. Robust T-cell and B-cell responses were elicited by a single injection of 2 x 10(5) infectious units, and responses were boosted following repeat immunizations. Anti-PSMA responses were detected following three immunizations with 10(2) infectious units and increased with increasing dose. PSMA-VRP was more immunogenic than adjuvanted PSMA protein. Responses to PSMA-VRP were characterized by Th-1 cytokines, potent CTL activity, and IgG2a/IgG2b antibodies. T-cell responses in BALB/c and C57BL/6 mice were directed toward different PSMA peptides. Immunogenic doses of PSMA-VRP were well tolerated in mice and rabbits. CONCLUSIONS: PSMA-VRP elicited potent cellular and humoral immunity in mice, and specific anti-PSMA responses were boosted on repeat dosing. PSMA-VRP represents a promising approach for immunotherapy of prostate cancer.     

Long-term risk factor control after a cardiac rehabilitation programme.

This study examined the hypothesis that Phase II cardiac rehabilitation participants (CRP) had better long-term risk factor control, self-rated perception of health and return to work rates than non-participants (NP) between 18 and 36 months post myocardial infarction (MI). It was a comparative study in a 550 bed hospital. Approximately half of both groups did not achieve a total cholesterol (TC) of 5.5 mmol/L or less. Compared with NP, CRP were significantly more likely to have a TC < = 6.5 mmol/L (7% vs. 28%) (p = 0.006). NP with TC > 6.5 mmol/L were significantly less likely to be on treatment (p = 0.002). CRP were more likely to regularly exercise than NP (79% vs. 61%) (p = 0.038). The success rate for blood pressure targets, return to work rates and self-rated perception of health were similar in both groups. In conclusion, CRP had better long-term control of some risk factors than NP. The study provides comparative longer-term patient outcomes after an Australian cardiac rehabilitation (CR) programme and forms the basis for further outcome measurement.