Abstract 5584: DNA vaccine encoding prostatic acid phosphatase (PAP) elicits long-term T-cell responses in patients with recurrent prostate cancer

Abstract

Abstract Prostatic acid phosphatase (PAP) is a tumor antigen in prostate cancer, and several clinical trials have used this as a tissue-specific target for anti-tumor vaccines. 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 encoding PAP and have previously reported the results of a phase I trial in which 22 patients with biochemically recurrent prostate cancer (clinical stage D0) were immunized six times at biweekly intervals using a DNA vaccine encoding PAP (pTVG-HP). In previous reports we identified that PAP-specific T-cells were elicited, including PAP-specific cytolytic T cells, two weeks following the six immunizations. In the current study we investigated the immunological efficacy of subsequent booster immunizations in two individuals, and conducted more detailed immunological analysis by IFNγ ELISPOT and T cell proliferation, with cells obtained prior to immunization, after every two immunizations, and quarterly for one year following immunization. These studies were conducted to determine when immune responses were elicited, and whether these responses were durable over time, to guide the schedule of vaccine administration to be used in future clinical trials with this particular DNA vaccine. We found that the majority of immune responses elicited with vaccination were only detectable after four to six immunizations. In addition, PAP-specific T-cell responses did persist in several individuals for many months, or were detectable only after several months. Finally, we identified that immune responses previously elicited could be further amplified by subsequent booster immunizations months later. These results suggest that future trials using this DNA vaccine, and potentially other anti-tumor DNA vaccines, should investigate ongoing, rather than limited, schedules of administration with periodic booster immunizations. Moreover, these results suggest that DNA vaccines targeting PAP could potentially be combined with other vaccine strategies targeting this particular antigen to augment PAP-specific T-cell immunity. A pilot trial to evaluate different schedules of DNA vaccine administration for the establishment of persistent PAP-specific memory T cells is currently underway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5584.