Safety and Immunological Efficacy of a DNA Vaccine Encoding Prostatic Acid Phosphatase in Patients With Stage D0 Prostate Cancer

Genitourinary Cancer
Purpose: Prostatic acid phosphatase (PAP) is a prostate tumor antigen. We have previously demonstrated that a DNA vaccine encoding PAP can elicit antigen-specific CD8+ T cells in rodents. We report here the results of a phase I/IIa trial conducted with a DNA vaccine encoding human PAP in patients with stage D0 prostate cancer.

Patients and Methods Twenty-two patients were treated in a dose-escalation trial with 100 µg, 500 µg, or 1,500 µg plasmid DNA, coadministered intradermally with 200 µg granulocyte-macrophage colony-stimulating factor as a vaccine adjuvant, six times at 14-day intervals. All patients were observed for 1 year after treatment.

Results: No significant adverse events were observed. Three (14%) of 22 patients developed PAP-specific IFN-secreting CD8+ T-cells immediately after the treatment course, as determined by enzyme-linked immunospot. Nine (41%) of 22 patients developed PAP-specific CD4+ and/or CD8+ T-cell proliferation. Antibody responses to PAP were not detected. Overall, the prostate-specific antigen (PSA) doubling time was observed to increase from a median 6.5 months pretreatment to 8.5 months on-treatment (P = .033), and 9.3 months in the 1-year post-treatment period (P = .054).

Conclusion: The demonstration that a DNA vaccine encoding PAP is safe, elicits an antigen-specific T-cell response, and may be associated with an increased PSA doubling time suggests that a multi-institutional phase II trial designed to evaluate clinical efficacy is warranted.

Supported by Grant No. K23 RR16489 from the National Institutes of Health (NIH; D.G.M., E.J.D.), by a production grant from the NIH National Gene Vector Laboratory Program, by the NIH National Center for Research Resources Clinical and Translational Science Award program (1UL1RR025011), and Grant No. W81XWH-05-1-0404 from the US Army Medical Research and Materiel Command Prostate Cancer Research Program (D.G.M., E.J.D., J.G.D., D.L.H., J.C.E.).


C. G. Drake
Immunotherapy for Prostate Cancer: Walk, Don't Run
J. Clin. Oncol., September 1, 2009; 27(25): 4035 - 4037.