Clinical StudiesDNA Vaccine Encoding Prostatic Acid Phosphatase (PAP) Elicits Long-term T-cell Responses in Patients With Recurrent Prostate CancerBecker, Jordan T.; Olson, Brian M.; Johnson, Laura E.; Davies, James G.; Dunphy, Edward J.; McNeel, Douglas G.Author Information Department of Medicine, University of Wisconsin Carbone Comprehensive Cancer Center, Madison, WI This study was supported by NIH (K23 RR16489), by the NIH National Gene Vector Laboratory Program, by the NIH NCRR Clinical and Translational Science Award (CTSA) program (1UL1RR025011), and by the US Army Medical Research and Materiel Command Prostate Cancer Research Program (W81XWH-05-1-0404). All authors have declared that there are no financial conflicts of interest in regards to this study. Reprints: Douglas G. McNeel, 7007 Wisconsin Institutes for Medical Research, 1111 Highland Avenue, Madison, WI 53705 (e-mail: email@example.com). Received for publication January 5, 2010; accepted March 7, 2010 Journal of Immunotherapy: July-August 2010 - Volume 33 - Issue 6 - p 639-647 doi: 10.1097/CJI.0b013e3181dda23e Buy Metrics Abstract Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer and the target of several anti-tumor vaccines in earlier clinical trials. Ultimately, the goal of anti-tumor vaccines is to elicit a sustainable immune response, able to eradicate a tumor, or at least restrain its growth. We have investigated plasmid DNA vaccines and have previously conducted a phase 1 trial in which patients with recurrent prostate cancer were vaccinated with a DNA vaccine encoding PAP. In this study, we investigated the immunologic efficacy of subsequent booster immunizations, and conducted more detailed longitudinal immune analysis, to answer several questions aimed at guiding optimal schedules of vaccine administration for future clinical trials. We report that antigen-specific cytolytic T-cell responses were amplified after immunization in 7 of 12 human leukocyte antigen-A2-expressing individuals, and that multiple immunizations seemed necessary to elicit PAP-specific interferon-γ-secreting immune responses detectable by enzyme-linked immunosorbent spot assay. Moreover, among individuals who experienced a ≥200% increase in prostate-specific antigen doubling time, long-term PAP-specific interferon-γ-secreting T-cell responses were detectable in 6 of 8, but in only 1 of 14 individuals without an observed change in prostate-specific antigen doubling time (P=0.001). Finally, we identified that immune responses elicited could be further amplified by subsequent booster immunizations. These results suggest that future trials using this DNA vaccine, and potentially other anti-tumor DNA vaccines, could investigate ongoing schedules of administration with periodic booster immunizations. Moreover, these results suggest that DNA vaccines targeting PAP could potentially be combined in heterologous immunization strategies with other vaccines to further augment PAP-specific T-cell immunity. © 2010 Lippincott Williams & Wilkins, Inc.