title: Combining a recombinant cancer vaccine with standard definitive radiotherapy in patients with localized prostate cancer.
abstract: OBJECTIVE
  Many patients with clinically localized prostate cancer develop biochemical failure despite excellent local therapy perhaps due to occult metastatic disease. One potential solution is the utilization of a well-tolerated systemic therapy (e.g., vaccine) in concert with local therapy.
  
  
  METHODS
  We present a randomized phase II clinical trial designed to determine if a poxviral vaccine encoding prostate-specific antigen (PSA) can induce a PSA-specific T-cell response when combined with radiotherapy in patients with clinically localized prostate cancer. Thirty patients were randomized in a 2:1 ratio into vaccine plus radiotherapy or radiotherapy-only arms. Those patients in the combination arm received a "priming" vaccine with recombinant vaccinia (rV) PSA plus r V containing the T-cell costimulatory molecule B7.1 (rV-B7.1) followed by monthly booster vaccines with recombinant fowlpox PSA. The vaccines were given with local granulocyte-macrophage colony-stimulating factor and low-dose systemic interleukin-2. Standard external beam radiation therapy was given between the fourth and the sixth vaccinations.
  
  
  RESULTS
  Seventeen of 19 patients in the combination arm completed all eight vaccinations and 13 of these 17 patients had increases in PSA-specific T cells of at least 3-fold versus no detectable increases in the radiotherapy-only arm (P < 0.0005). There was also evidence of de novo generation of T cells to well-described prostate-associated antigens not found in the vaccine, providing indirect evidence of immune-mediated tumor killing. The vaccine was well tolerated.
  
  
  CONCLUSIONS
  This vaccine regimen can be safely given in patients undergoing radiation therapy for localized prostate cancer, with the majority of patients generating a PSA-specific cellular immune response to vaccine.
authors.affiliation: Laboratory of Tumor Immunology and Biology, Medical Oncology Clinical Research Unit, Radiation Oncology Branch, and Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Philip M
authors.initials: PM
authors.lastname: Arlen
authors.forename: Anne
authors.initials: A
authors.lastname: Bastian
authors.forename: Steven
authors.initials: S
authors.lastname: Morin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Marte
authors.forename: Patricia
authors.initials: P
authors.lastname: Beetham
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Junko
authors.initials: J
authors.lastname: Yokokawa
authors.forename: James W
authors.initials: JW
authors.lastname: Hodge
authors.forename: Cynthia
authors.initials: C
authors.lastname: Ménard
authors.forename: Kevin
authors.initials: K
authors.lastname: Camphausen
authors.forename: C Norman
authors.initials: CN
authors.lastname: Coleman
authors.forename: Francis
authors.initials: F
authors.lastname: Sullivan
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: William
authors.initials: W
authors.lastname: Dahut
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018122:B7-1 Antigen / Q000235:genetics / Q000276:immunology; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D002460:Cell Line; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D006801:Humans; D008297:Male; D008875:Middle Aged; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000276:immunology / Q000532:radiotherapy / Q000628:therapy*; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000627:therapeutic use; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D018122:B7-1 Antigen; D019496:Cancer Vaccines; D011993:Recombinant Fusion Proteins; D017430:Prostate-Specific Antigen