title: A viral vaccine encoding prostate-specific antigen induces antigen spreading to a common set of self-proteins in prostate cancer patients.
abstract: OBJECTIVE
  We previously reported a randomized phase II clinical trial combining a poxvirus-based vaccine encoding prostate-specific antigen (PSA) with radiotherapy in patients with localized prostate cancer. Here, we investigate whether vaccination against PSA induced immune responses to additional tumor-associated antigens and how this influenced clinical outcome.
  
  
  METHODS
  Pretreatment and posttreatment serum samples from patients treated with vaccine + external beam radiation therapy (EBRT) versus EBRT alone were evaluated by Western blot and serologic screening of a prostate cancer cDNA expression library (SEREX) to assess the development of treatment-associated autoantibody responses.
  
  
  RESULTS
  Western blotting revealed treatment-associated autoantibody responses in 15 of 33 (45.5%) patients treated with vaccine + EBRT versus 1 of 8 (12.5%) treated with EBRT alone. SEREX screening identified 18 antigens, which were assembled on an antigen array with 16 previously identified antigens. Antigen array screening revealed that 7 of 33 patients (21.2%) treated with vaccine + EBRT showed a vaccine-associated autoantibody response to four ubiquitously expressed self-antigens: DIRC2, NDUFS1, MRFAP1, and MATN2. These responses were not seen in patients treated with EBRT alone, or other control groups. Patients with autoantibody responses to this panel of antigens had a trend toward decreased biochemical-free survival.
  
  
  CONCLUSIONS
  Vaccine + EBRT induced antigen spreading in a large proportion of patients. A subset of patients developed autoantibodies to a panel of four self-antigens and showed a trend toward inferior outcomes. Thus, cancer vaccines directed against tumor-specific antigens can trigger autoantibody responses to self-proteins, which may influence the efficacy of vaccination.
authors.affiliation: Trev & Joyce Deeley Research Centre, BC Cancer Agency-Vancouver Island Centre, 2410 Lee Avenue, Victoria, British Columbia, Canada.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Nesslinger
authors.forename: Alvin
authors.initials: A
authors.lastname: Ng
authors.forename: Kwong-Yok
authors.initials: KY
authors.lastname: Tsang
authors.forename: Theresa
authors.initials: T
authors.lastname: Ferrara
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Schlom
authors.forename: James L
authors.initials: JL
authors.lastname: Gulley
authors.forename: Brad H
authors.initials: BH
authors.lastname: Nelson
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000941:Antigens / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D003131:Combined Modality Therapy; D015870:Gene Expression; D020869:Gene Expression Profiling; D005822:Genetic Vectors; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011212:Poxviridae; D017430:Prostate-Specific Antigen / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology* / Q000401:mortality / Q000628:therapy*; D011878:Radiotherapy
chemical_list: D000941:Antigens; D000951:Antigens, Neoplasm; D001323:Autoantibodies; D019496:Cancer Vaccines; D017430:Prostate-Specific Antigen