Background:~Pox viral vectors can induce a PSA-specific T-cell responses and clinical responses in patients with advanced prostate cancer.~Intratumoral vaccines of recombinant fowlpox vectors appear to be more potent in inducing antitumor effects than the s.c. route of administration, especially when the recombinant rF-vector given intratumorally is preceded by a rV-recombinant given s.c. This may be due to:~Making the tumor cell an antigen presenting cell via upregulation of both antigen (signal 1) and costimulatory molecules (signal 2).~Making the tumor cell more susceptible to killing via upregulation of ICAM.~The increased expression of perforin in peptide-specific T cells that came into contact with the TRICOM-infected targets.~Potentially allowing the immune system to select for other tumor encoded antigens to generate a polyvalent immune response.~Objectives:~1: Safety and feasibility of an intraprostatic vaccine strategy.~2: To assess the change in PSA-specific T-cell response as measured by ELISPOT assay.~2: To evaluate T-cell infiltration histologically in patients who have pre- and post-vaccine prostate biopsies.~Eligibility:~Must have either a) biopsy proven, locally recurrent prostate cancer following local radiation as defined by the ASTRO consensus criteria as 3 consecutively rising PSA levels or b) have refused or not be candidates for local definitive therapy (surgery or radiation therapy) and have clinically progressive disease on androgen deprivation therapy (eg. three increases in PSA over nadir, separated by at least one week). For patients with previous RT, the biopsy confirming local recurrence must be done at least 18 months after the completion of RT.~Since this may also generate a systemic immune response, patients with minimal extraprostatic disease may be enrolled.~Hepatic function: Bilirubin less than 1.5 mg/dl, AST and ALT less than 2.5 times upper limit of normal.~Design:~Dose escalation Phase I design. Each cohort will consist of 3-6 patients; maximum accrual is 30~Patients in all cohorts receive initial priming with rV- PSA(L155)/TRICOM and rF-GM-CSF s.c.~The first two cohorts utilize a booster intraprostatic with dose escalation of rF-PSA(L155)/TRICOM.~Third and fourth cohorts add dose escalations of rF-GM-CSF along with the highest dose of rF-PSA(L155)/TRICOM.~Last (5th) cohort utilizes booster intraprostatic vaccine (rF-PSA(L155)/TRICOM and rF-GM-CSF) with simultaneous identical booster vaccine given s.c.
Background:~Pox viral vectors can induce a PSA-specific T-cell responses and clinical responses in patients with advanced prostate cancer.~Intratumoral vaccines of recombinant fowlpox vectors appear to be more potent in inducing antitumor effects than the s.c. route of administration, especially when the recombinant rF-vector given intratumorally is preceded by a rV-recombinant given s.c. This may be due to:~Making the tumor cell an antigen presenting cell via upregulation of both antigen (signal 1) and costimulatory molecules (signal 2).~Making the tumor cell more susceptible to killing via upregulation of ICAM.~The increased expression of perforin in peptide-specific T cells that came into contact with the TRICOM-infected targets.~Potentially allowing the immune system to select for other tumor encoded antigens to generate a polyvalent immune response.~Objectives:~1: Safety and feasibility of an intraprostatic vaccine strategy.~2: To assess the change in PSA-specific T-cell response as measured by ELISPOT assay.~2: To evaluate T-cell infiltration histologically in patients who have pre- and post-vaccine prostate biopsies.~Eligibility:~Must have either a) biopsy proven, locally recurrent prostate cancer following local radiation as defined by the ASTRO consensus criteria as 3 consecutively rising PSA levels or b) have refused or not be candidates for local definitive therapy (surgery or radiation therapy) and have clinically progressive disease on androgen deprivation therapy (eg. three increases in PSA over nadir, separated by at least one week). For patients with previous RT, the biopsy confirming local recurrence must be done at least 18 months after the completion of RT.~Since this may also generate a systemic immune response, patients with minimal extraprostatic disease may be enrolled.~Hepatic function: Bilirubin < 1.5 mg/dl, AST and ALT< 2.5 times upper limit of normal~Design:~Dose escalation Phase I design. Each cohort will consist of 3-6 patients, with cohorts 4 & 5 restricted to include only HLA-A2 + patients; maximum accrual is 30~Patients in all cohorts receive initial priming with rV- PSA(L155)/TRICOM and rF-GM-CSF s.c.~The first two cohorts utilize a booster intraprostatic with dose escalation of rF-PSA(L155)/TRICOM.~Third and fourth cohorts add dose escalations of rF-GM-CSF along with the highest dose of rF-PSA(L155)/TRICOM~Last (5th) cohort u...