Phase I study of a DNA-based vaccine targeting prostatic acid phosphatase (PAP) in patients with clinical stage D0 prostate cancer

1858 Background: Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer. Clinical trials conducted in patients with metastatic prostate cancer targeting PAP by means of antigen presenting-cell vaccines have suggested clinical benefit in terms of disease progression and overall survival. Ultimately, however, tumor vaccines may be most effective in the setting of minimal residual disease. We have investigated plasmid DNA vaccines encoding PAP in rodent models. We found these to be safe and effective in eliciting PAP-specific CD8+ T cells and observed evidence of anti-tumor efficacy. We report here the initial clinical and immunological results from a dose-escalation phase I trial evaluating a DNA vaccine encoding PAP in patients with minimal residual prostate cancer, clinical stage D0. Methods: Patients with clinical stage D0 prostate cancer with rising serum PSA were vaccinated over a 12-week period, six times at 14-day intervals, with a plasmid DNA vaccine encoding PAP (pTVG-HP) in a dose-escalation trial. Vaccinations were administered intradermally with 100 mcg, 500 mcg, or 1500 mcg doses, and with 200 mcg of GM-CSF co-administered as a vaccine adjuvant. The primary endpoints of the trial were safety and immunological response, antigen-specific IFNγ-secreting CD8+ T cells as measured by ELISPOT. Other immunological responses were evaluated by antigen-specific T cell proliferation and IFNγ secretion and by ELISA for PAP-specific IgG. Results: Nine patients were enrolled and all completed the immunization series. No serious adverse events were observed, and no events greater than grade 2 were identified. Antibody responses to PAP were not observed, however 4/9 developed PAP-specific CD4+ or CD8+ proliferative T cell responses. 2/9 patients developed PAP-specific IFNγ-secreting CD8+ T cells, detectable without in vitro stimulation, as measured by ELISPOT, the primary immunological endpoint of the trial. 2/9 patients also demonstrated a marked increase in PSA doubling time, one of whom was found to have an ELISPOT response. Conclusions: Intradermal immunization of patients with stage D0 prostate cancer with pTVG-HP resulted in no significant adverse events in doses up to 1500 mcg. CD4+ and CD8+ T cell responses were elicited, consistent with a predominantly cellular immune response, at even the lowest dose of vaccine. The development of an antigen-specific CD8+ T cell response in conjunction with an increase in PSA doubling time in some patients suggests that further clinical evaluation is warranted.