Purpose: Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy. Experimental Design:We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapyonly arms. Those patients in the combination arm received a ''priming'' vaccine with recombinant vaccinia (r V) PSA plus r V containing theT-cell costimulatory molecule B7.1 (r V-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor andlow-dose systemicinterleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations. Results: Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specificTcells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P <0.0005).There was also evidence ofde novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated. Conclusion:This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.

BACKGROUNDA Phase I trial of recombinant vaccinia prostate specific antigen (rV‐PSA) in patients with advanced metastatic prostate cancer was conducted. This report describes 42 patients who were treated with up to three monthly vaccinations.METHODSAll patients were entered on a dose‐escalation phase I study of recombinant vaccinia containing the gene for PSA (rV‐PSA). The primary objective of this study was to determine the safety of this vaccine in metastatic androgen‐independent prostate cancer patients. A secondary objective was to assess evidence of anti‐tumor activity by PSA measurements, radiologic findings, and immunologic methods.RESULTSThere was no significant treatment‐related toxicity apart from erythema, tenderness, and vesicle formation that lasted several days at the site of injection in some patients. There were immunologic responses, in selected patients, as evidenced by an increase in the proportion of PSA‐specific T cells after vaccination. Furthermore, we show that these patients' T cells can lyse PSA‐expressing tumor cells in vitro.CONCLUSIONGiven the low toxicity profile and the evidence of immunologic activity, we believe future study is warranted with PSA‐based vaccines in prostate cancer. New PSA‐based vaccines and vaccine strategies are currently being evaluated. Prostate 53: 109–117, 2002. © 2002 Wiley‐Liss, Inc.

Further studies are merited to investigate the role of combining vaccine with antiandrogen therapy or vaccine followed by vaccine plus antiandrogen therapy in this patient population.