PSA-Activated PSA-PAH1 for Locally Recurrent Prostate Cancer

Inclusion Criteria: * 18 years of age or older * Histologically proven prostate adenocarcinoma * Completed a full course of definitive external beam radiation or definitive brachytherapy (but not both) as primary therapy for diagnosed prostate cancer at least one year prior to enrollment * Subject must have at least one available PSA measurement that was taken 60 days or more following their primary therapy, but no later than 2 months prior to their screening visit (this measurement will serve as the first time point for computing a screening value for PSA doubling time) * Subject's PSA doubling time at screening must be \> 3 months (this doubling time will be computed by comparing the earliest available PSA that is 60 days or more following the subject's primary therapy but no later than 2 months prior to their screening visit, to the PSA measurement obtained during the screening visit) * Within one year prior to enrollment: * Demonstrated "biochemical failure," as determined by three consecutive increases in PSA at least 2 weeks apart * Multiple-site biopsy-confirmed local recurrence of prostate cancer * Within 3 months prior to enrollment: * No evidence of metastatic disease including no bone metastases on bone scan, or any lymph node, lung, liver or soft tissue metastases on a CT or MRI scan or any other evidence of metastatic disease * No receipt of androgen ablation therapy \[Note: Subjects may have received androgen ablation therapy in the past, but not within 3 months prior to enrollment. No subject will be removed from androgen ablation therapy prior to this trial to permit/facilitate eligibility for this trial.\] * Within 30 days prior to enrollment: * Prostate gland weighing less than 40 g estimated on the basis of CT/ultrasound data * Serum testosterone above castrate range (\> 1 ng/dL) * PSA level less than 20 ng/mL * Eastern Cooperative Oncology Group (ECOG) score of 0-2 * Written informed consent * Adequate organ function as evidenced by: Exclusion Criteria: * Any history of active malignancy other than prostate cancer * Have active viral, bacterial or fungal infections that require systemic therapy * Prior biological, immunological or chemotherapy for prostate cancer * Receiving concurrent medication for prostate cancer * Received as primary therapy for prostate cancer, definitive external beam radiation and concomitant brachytherapy * Prior history of metastatic prostate cancer * Treatment with other investigational therapies within 12 months prior to enrollment that could produce a compromised immune system, or receipt of immunosuppressive drugs including corticosteroids or ketoconazole within 1 month prior to enrollment, or a history of immunodeficiency disease * Recurrence of prostate cancer within 6 months after initiation of primary radiotherapy * Active heart, liver, lung, renal disease, active infection or other serious uncontrolled illnesses * Positive antibody test during screening for HIV-1, HIV-2, HTLV-1, HTLV-2, Hep B, or Hep C * Unable or unwilling to return for required visits and follow-up examinations * Have a chronic indwelling Foley catheter for obstructive uropathy * Received salvage external beam radiotherapy and/or salvage seed brachytherapy prior to enrollment * Received prior treatment with PSA-PAH1 (subjects may not be redosed under this protocol) * Men unwilling to use condoms for the duration of the study (3 months) to prevent a pregnancy, and to avoid semen contact with their partner.