title: Tumor-reactive CD8+ T-cell responses after vaccination with NY-ESO-1 peptide, CpG 7909 and Montanide ISA-51: association with survival.
abstract: Peptide-based vaccines have led to the induction of antigen-specific CD8(+) T-cell responses in patients with NY-ESO-1 positive cancers. However, vaccine-induced T-cell responses did not generally correlate with improved survival. Therefore, we tested whether a synthetic CpG 7909 ODN (deoxycytidyl-deoxyguanosin oligodeoxy-nucleotides) mixed with NY-ESO-1 peptide p157-165 and incomplete Freund's adjuvants (Montanide(R) ISA-51) led to enhanced NY-ESO-1 antigen-specific CD8(+) immune responses in patients with NY-ESO-1 or LAGE-1 expressing tumors. Of 14 HLA-A2+ patients enrolled in the study, 5 patients withdrew prematurely because of progressive disease and 9 patients completed 1 cycle of immunization. Nine of 14 patients developed measurable and sustained antigen-specific CD8(+) T-cell responses: Four had detectable CD8+ T-cells against NY-ESO-1 after only 2 vaccinations, whereas 5 patients showed a late-onset but durable induction of NY-ESO-1 p157-165 specific T-cell response during continued vaccination after 4 months. In 6 patients, vaccine-induced antigen-specific T-cells became detectable ex vivo and reached frequencies of up to 0.16 % of all circulating CD8(+) T-cells. Postvaccine T-cell clones were shown to recognize and lyse NY-ESO-1 expressing tumor cell lines in vitro. In 6 of 9 patients developing NY-ESO-1-specific immune responses, a favorable clinical outcome with overall survival times of 43+, 42+, 42+, 39+, 36+ and 27+ months, respectively, was observed.
authors.affiliation: Klinik für Onkologie und Hämatologie, Krankenhaus Nordwest, Frankfurt, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Karbach
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Armin
authors.initials: A
authors.lastname: Bender
authors.forename: Antje
authors.initials: A
authors.lastname: Neumann
authors.forename: Eckhart
authors.initials: E
authors.lastname: Weidmann
authors.forename: Jianda
authors.initials: J
authors.lastname: Yuan
authors.forename: Cathy A
authors.initials: CA
authors.lastname: Ferrara
authors.forename: Eric
authors.initials: E
authors.lastname: Hoffmann
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Nasser K
authors.initials: NK
authors.lastname: Altorki
authors.forename: Elke
authors.initials: E
authors.lastname: Jäger
mesh_terms: D000951:Antigens, Neoplasm / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000276:immunology / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008353:Mannitol / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008545:Melanoma / Q000276:immunology; D008565:Membrane Proteins / Q000627:therapeutic use*; D009367:Neoplasm Staging; D009369:Neoplasms / Q000276:immunology*; D009829:Oleic Acids / Q000627:therapeutic use*; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use*; D010051:Ovarian Neoplasms / Q000276:immunology / Q000473:pathology; D012509:Sarcoma / Q000276:immunology / Q000473:pathology; D014611:Vaccination / Q000379:methods*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D008565:Membrane Proteins; D009829:Oleic Acids; D009838:Oligodeoxyribonucleotides; C483020:ProMune; C477385:montanide ISA 51; D008353:Mannitol