2. OBJECTIVES 2.1 Primary Objective To evaluate the development of anti -PSA immune responses in study patients, of particular importance is the comparison of immune responses generated in the hormone naïve and ADT patients. 2.2 Secondary objectives 2.2.1 To evaluate the response rates (PSA responses and changes in PSADT) of the Ad/PSA vaccine using a prime-boost immunization strategy, in patients with recurrent disease, either hormone naïve or during androgen deprivation therapy (ADT). 2.2.2 To evaluate biochemical (PSA recurrence) and radiographic (bone scans) time to progression and overall survival in evaluable patients receiving the Ad/PSA vaccine. PROTOCOL #1 Lubaroff, page 15 3. SELECTION OF PATIENTS As described in Section 1.6 prostate cancer patients will be enrolled in one of two arms of the study. All men will have recurrent disease and who are considered hormone naïve, having received no prior hormonal therapy except as allowed in section 3.2.9. Following the determination of eligibility to participate in the protocol, one group of patients will receive the Ad/PSA vaccine alone ( Arm A) and a second group of patients will begin androgen deprivation therapy with vaccination beginning fourteen days later (Arm B). 3.1 Inclusion criteria: 3.1.1 Men with prostate cancer who have received prior local therapy (radical prostatecto my or definitive radiation therapy) and have biochemical (PSA) relapse without evidence of radiographic or clinical metastatic disease. 3.1.2 For men who had prior prostatectomy, the surgery must have occurred at least 6 months prior to initiation of treatment. 3.1.3 For men who had prior definitive radiation therapy, radiation must have been completed at least 1 year prior to initiation of treatment. 3.1.4 Exhibit at least three separate rises in serum PSA, at least one month apart with differences >0.03 ng/ml and a total PSA of >0.2 ng/ml . 3.1.5 Have a PSA doubling time of > 6 months if the baseline serum PSA was >2 ng/ml . 3.1.6 Negative bone scans. 3.1.7 Negative CT scans of abdomen and pelvis (no evidence of soft tissue lesions >1 cm). 3.1.8 Scans must be obtained within 6 weeks of entry into the trial (initiation of treatment). 3.1.9 Written informed consent. 3.1.10 Age > 18 years. 3.1.11 R equired laboratory values [ obtained within 2 weeks of study entry (initiation of treatment)] 3.1.12.1 Serum creatinine < 2.0 mg/dL 3.1.12.2 Adequate hematologic function: granulocytes > 1800 per mm3, platelets > 100,000 per mm3, WBC >3700, and lymphocytes > 590. 3.1.12.3 Adequate hepatocellular function: AST <3x ULN and total bilirubin <1.5 mg/dl (unless bilirubin elevation is consistent with Gilbert’s syndrome) . PROTOCOL #1 Lubaroff, page 16 3.1.13 PSA used as an eligibility criterion must be drawn within 42 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 Candidates for salvage radiation therapy unless the patient refuses. 3.2.2 Active or unresolved clinically significant infection. 3.2.3 Parenteral antibiotics <7 days prior to initiation of treatment. 3.2.4 Evidence of prior or current CNS metastases. Specific imaging is not necessary in the absence of signs or symptoms. 3.2.5 Co-morbid medical conditions which would result in a life expectancy (participation) of less than 1 year. 3.2.6 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 the last 3 months is not allowed. 3.2.7 Pre-existing mali gnancies that required treatment within the past 5 years except for basal or squamous cell cancers of the skin. 3.2.8 Prior systemic therapies for prostate cancer not allowed (hormonal therapy, including but not limited to LHRH agonists, antiandrogens, ketoconazole or chemotherapy – mitoxantrone/taxanes/estramustine, etc.) except when patients stopped hormone therapy two or more years prior to enrollment and currently have normal testosterone levels; patients in Arm B, undergoing androgen depletion therapy during the vaccination study will be eligible. 3.2.9 Prior participation in any vaccine studies for non -infectious diseases.