title: Clinical safety of a viral vector based prostate cancer vaccine strategy.
abstract: OBJECTIVE
  The primary objective of this phase I study was to evaluate the clinical safety of a vaccine using recombinant vaccinia virus (prime) and recombinant fowlpox virus (boost) in combination with granulocyte-macrophage colony-stimulating factor in patients with prostate cancer. The vaccines contained transgenes for prostate specific antigen, a triad of co-stimulatory molecules and a tumor antigen whose amino acid sequence had been modified to enhance its immunogenicity. Secondary end points were immunological and clinical responses, changes in prostate specific antigen velocity, and the kinetics of vaccinia virus clearance from the vaccination site, serum, peripheral blood mononuclear cells, urine and saliva.
  
  
  METHODS
  The 15 patients enrolled in this study had metastatic prostate cancer. Patients were given recombinant fowlpox-prostate specific antigen/triad of co-stimulatory molecules alone or recombinant vaccinia-prostate specific antigen/triad of co-stimulatory molecules followed by recombinant fowlpox-prostate specific antigen/triad of co-stimulatory molecules on a prime and boost schedule with or without recombinant-granulocyte-macrophage colony-stimulating factor protein or recombinant fowlpox-granulocyte-macrophage colony-stimulating factor vector. Prostate specific antigen specific immune responses were measured using an enzyme-linked immunosorbent spot assay for interferon-gamma production. Polymerase chain reaction for vaccinia DNA and a plaque assay for live virus were also used.
  
  
  RESULTS
  Some grade 2 toxicity was seen in patients who received a higher dose of recombinant fowlpox-granulocyte-macrophage colony-stimulating factor but no toxicity exceeded grade 2. Viable vaccinia was detected after vaccination at the site swab of 1 of 4 patients analyzed. Prostate specific antigen specific immune responses were seen in 4 of 6 patients who were HLA-A2+ and decreases in serum prostate specific antigen velocity were observed in 9 of 15.
  
  
  CONCLUSIONS
  Based on the safety and preliminary immunogenicity results of this trial we recommend initiating a randomized, phase II study of prostate specific antigen/triad of co-stimulatory molecules vaccines in patients with less advanced prostate cancer.
authors: Laboratory of Tumor Immunology and Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors: Philip M
authors: PM
authors: Arlen
authors: Lisa
authors: L
authors: Skarupa
authors: Mary
authors: M
authors: Pazdur
authors: Mahesh
authors: M
authors: Seetharam
authors: Kwong Y
authors: KY
authors: Tsang
authors: Douglas W
authors: DW
authors: Grosenbach
authors: Jarett
authors: J
authors: Feldman
authors: Diane J
authors: DJ
authors: Poole
authors: Mary
authors: M
authors: Litzinger
authors: Seth M
authors: SM
authors: Steinberg
authors: Elizabeth
authors: E
authors: Jones
authors: Clara
authors: C
authors: Chen
authors: Jennifer
authors: J
authors: Marte
authors: Howard
authors: H
authors: Parnes
authors: John
authors: J
authors: Wright
authors: William
authors: W
authors: Dahut
authors: Jeffrey
authors: J
authors: Schlom
authors: James L
authors: JL
authors: Gulley
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019496:Cancer Vaccines / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D018450:Disease Progression; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000276:immunology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology; D014614:Vaccines, Synthetic / Q000009:adverse effects / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D014614:Vaccines, Synthetic; C479602:rF-TRICOM vaccine; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D017430:Prostate-Specific Antigen