J. Brown and M. O’Donnell and ARNP E. Brown will assist in the recruitment of patients from the Department of Urology, Dr. Vaena from Internal Medicine, and Dr. Smith from Radiation Oncology. Additional recruitment of patients will occur through a collaboration with Mercy Medical Center, Des Moines, IA (Hereafter referred to as DMMCC). Once accrual has been completed, no further recruitment methods will be utilized. A physician from outside the UIHC or ICVAHCS may inform patients of the study. If a patient expresses interest in learning more about the trial, the physician will provide him with contact information for the clinical trial team. When a patient contacts the clinical trial team, a member of the trial team will briefly describe the study and request the patient’s mailing address in order to mail him a copy of the study informed consent form. After the patient has had time to become familiar with the study and discuss it with his family, a member of the research team will follow up with a telephone call to discuss the study and answer any questions the patient may have. At this time, if the patient is still interested in participating, he will be asked to provide verbal consent to allow the research team to review information from his medical record to evaluate his eligibility for the trial. The researcher will document the verbal consent process in the research file, and will contact the patient’s physician to request the medical record for review. The patient will be required to sign a HIPAA privacy form and a Release of Medical Information form at his physician’s office prior to the physician releasing his records to the research team. After reviewing the relevant portions of the medical record, a member of the research team will again contact the patient. Eligible individuals will be scheduled for a visit to the UIHC or ICVAHCS to undergo additional eligibility testing. At that visit, informed consent for participation in the clinical trial will be obtained. The subject will then be further evaluated for study eligibility Lubaroff Ad/PSA Phase II, protocol #2, page 14 through a medical history and physical exam, blood tests, and scans. Final determination of eligibility will occur at a weekly meeting of the clinical trial team. 2. OBJECTIVES 2.1 Primary Objective To evaluate the response rates (PSA responses and changes in PSADT) following immunization with the Ad/PSA vaccine using a prime-boost immunization s trategy, in patients with hormone refractory metastatic disease. 2.2 Secondary objectives 2.2.1 To evaluate the development of anti -PSA immune responses in study patients. 2.2.2 To evaluate biochemical (PSA recurrence) and radiographic (bone scans) time to progr ession and overall survival in evaluable patients recei ving the Ad/PSA vaccine. 3. SELECTION OF PATIENTS As described in Section 1.6 prostate cancer patients with hormone refractory metastatic disease will be enrolled in the study. 3.1 Inclusion criteri a: 3.1.1 Men with prostate cancer who present with evidence of hormone refractory disease (D3) . 3.1.2 Men with a positive bone scan or a positive CT scan (with obvious soft tissue metastasis or lymph nodes >1 cm), a PSA doubling time of >6 months, and a total PSA of <10 ng/ml, and asymptomatic OR men with a negative bone scan and a negative CT scan with any PSA doubling time and asymptomatic. 3.1.3 Scans must be obtained within 6 weeks of initiation of treatment. 3.1.4 Written informed consent. 3.1.5 Age > 18 years. 3.1.6 R equired laboratory values (obtained within 2 weeks of initiation of treatment) 3.1.6 .1 Serum creatinine < 2.0 mg/dL 3.1.6 .3 Adequate hematologic function: granulocytes > 1800 per mm3, platelets > 100,000 per mm3, WBC >3700, and lymphocytes > 590. 3.1.6 .4 Adequate hepatocellular function: AST <3x ULN and total bilirubin <1.5 mg/dl (unless bilirubin elevation is consistent with Gilbert’s syndrome) . Lubaroff Ad/PSA Phase II, protocol #2, page 15 3.1.6 .5 Castrate levels of testosterone of <50 ng/ml. 3.1.7 PSA used as an eligibility criterion must be drawn within 28 days prior to injection number 1 and will be redrawn on Day 1 for use as a baseline value. 3.2 Exclusion criteria: 3.2.1 Active or unresolved clinically significant infection. 3.2.2 Parenteral antibiotics <7 days prior to initiation of treatment. 3.2.3 Evidence of prior or current CNS metastas es. Specific imaging is not necessary in the absence of signs or symptoms. 3.2.4 Co-morbid medical conditions which would result in a life expectancy (parti cipation) of less than 1 year. 3.2.5 Patients with compromised immune systems; congenital, acquired, or drug- induced (immunosuppressive agents) will be excluded from the study. Use of prednisone at doses higher than 10 mg daily (or equipotent steroid doses) for more than 7 days within 3 months of initiation of treatment is not allowed. 3.2.6 Pre-existing malignancies that required treatment within the past 5 years except for basal or squamous cell cancers of the skin. 3.2.8 Prior participation in any vaccine studies for non -infectious diseases. 3.2.9 Prior chemotherapy, defined as prior cytotoxic chemotherapy for prostate cancer (or any cancer unless more than 5 years have elapsed). Examples of cytotoxic chemotherapy are mitoxantrone/prednisone and taxanes. Drugs such as Casodex or ketoconazole treatment must have been completed at least 6 weeks prior to initiation of treatment. 3.2.10 The inability to understand the English language and the clinical protocol. 3.2.11 Allergy or religious objection to pork products; Gelfoam is produced from pork. Patients that have been on bisphosphonate treatment for greater than 1 month prior to entry into the trial will be able to continue the medication. Patients that have not been on bisphosphonate therapy will not start on the medication for at least 30 days after the first vaccination. 4. Registration Procedures 4.1 All patients will be registered through the Department of Urology at the University of Iowa Hospitals and Clinics (UIHC) or the Urology S ervice at the Iowa City Veterans Affairs Health Care System (ICVAHCS ). 4.2 Patients who are candidates for enrollment into the study will be evaluated for eligibility by the clinical investigators to ensure that the criteria outlined in Section 3 have been satisfied and that the patient is eligible for participation in this clinical investigation. The University of Iowa will provide a patient eligibility case report form for this evaluation. Lubaroff Ad/PSA Phase II, protocol #2, page 16 4.3 Informed Consent - Signed informed consent for enrollment in this protocol will be obtained from eligible patients by the attending physician, study coordinator, or clinical trial coordinator before the start of research intervention. At the preadmission consultation, patients will be fully informed of the purpose and potential risks and benefits of participating in the study. Patients have the opportunity to have questions answered to their satisfaction before signing the consent. 4.4 Eligible patients must be registered Monday through Friday between 8:00 a.m. and 4:30 p.m.