title: Efficient in vivo priming by vaccination with recombinant NY-ESO-1 protein and CpG in antigen naive prostate cancer patients.
abstract: OBJECTIVE
  NY-ESO-1, one of the most immunogenic tumor antigens, is expressed in 15% to 25% of metastatic prostate cancers. The immunological and clinical effects of vaccination with recombinant NY-ESO-1 protein combined with CpG as adjuvant were evaluated.
  
  
  METHODS
  In a phase I clinical study, patients with advanced prostate cancer were vaccinated with recombinant NY-ESO-1 protein (100 μg) mixed with CpG 7909 (2.5 mg) every 3 weeks intradermally for 4 doses. Objectives of the study were the safety of the vaccine and changes of specific humoral and cellular immunological responses to NY-ESO-1 in relation to detectable NY-ESO-1 expression in the individual tumor.
  
  
  RESULTS
  All 12 baseline sero-negative patients developed high-titer NY-ESO-1 antibody responses. B-cell epitope mapping identified NY-ESO-1 p91-110 to be recognized most frequently by vaccine-induced antibodies. Two patients developed significant antibody titers against the adjuvant CpG. NY-ESO-1-specific CD4+ and/or CD8+ T-cell responses were induced in 9 patients (69%). Five of these 9 patients did not express NY-ESO-1 in the autologous tumor. Postvaccine CD8+ T-cell clones recognized and lyzed HLA-matched tumor cell lines in an antigen-specific manner.
  
  
  CONCLUSIONS
  Our data provide clear evidence for the capacity of NY-ESO-1 protein/CpG vaccine to induce integrated antigen-specific immune responses in vivo and to efficiently prime CD8+ T-cell responses in NY-ESO-1 antigen-negative patients. Our results may also support further clinical vaccination protocols with NY-ESO-1 protein not only focused on the treatment of existing cancer, but also to prevent further development of NY-ESO-1 positive cancers in vivo.
authors.affiliation: II. Medizinische Klinik, Hämatologie - Onkologie, Krankenhaus Nordwest, Frankfurt, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Karbach
authors.forename: Antje
authors.initials: A
authors.lastname: Neumann
authors.forename: Akin
authors.initials: A
authors.lastname: Atmaca
authors.forename: Claudia
authors.initials: C
authors.lastname: Wahle
authors.forename: Kathrin
authors.initials: K
authors.lastname: Brand
authors.forename: Lotta
authors.initials: L
authors.lastname: von Boehmer
authors.forename: Alexander
authors.initials: A
authors.lastname: Knuth
authors.forename: Armin
authors.initials: A
authors.lastname: Bender
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
mesh_terms: D056704:Adaptive Immunity; D000276:Adjuvants, Immunologic / Q000008:administration & dosage* / Q000009:adverse effects; D000951:Antigens, Neoplasm / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D006801:Humans; D007271:Injections, Intradermal; D008297:Male; D008565:Membrane Proteins / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D011471:Prostatic Neoplasms / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins; D009838:Oligodeoxyribonucleotides; C483020:ProMune