The Prostate 53:109 ^117 (2002) Phase I Study of aVaccine Using Recombinant Vaccinia Virus Expressing PSA (rV-PSA) in Patients With Metastatic Androgen-Independent Prostate Cancer James Gulley, 1,2 Alice P. Chen, 1 William Dahut, 1 Philip M. Arlen, 1,2 Anne Bastian, 1 Seth M. Steinberg, 3 Kwong Tsang, 2 Dennis Panicali, 4 Diane Poole, 2 Jeffrey Schlom, 2 * and J. Michael Hamilton 1 1 Medical Oncology Clinical Research Unit,Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 2 Laboratory of Tumor Immunology and Biology,Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 3 Biostatistics and Data Management Section,Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 4 Therion Biologics Corporation,Cambridge, Massachusetts BACKGROUND. A 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. METHODS. All 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. RESULTS. There 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. CONCLUSION. Given 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. KEY WORDS: PSA; vaccine; prostate cancer; T cells INTRODUCTION Prostate cancer is the most common noncutaneous malignancy among American men (189,000 cases estimated in 2002) and is the second most common cause of cancer death in men (32,200 deaths) [1]. Although more patients are now diagnosed with localized prostate cancer since the advent of PSA *Correspondence to: Jeffrey Schlom, Laboratory of Tumor Immu- nology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Room 8B09, Bethesda, MD 20892. E-mail: js141c@nih.gov Received 6 December 2001; Accepted 27 April 2002 DOI 10.1002/pros.10130 ß 2002 Wiley-Liss, Inc.