title: Recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant induces broad integrated antibody and CD4(+) and CD8(+) T cell responses in humans.
abstract: NY-ESO-1 is a "cancer-testis" antigen expressed in many cancers. ISCOMATRIX is a saponin-based adjuvant that induces antibody and T cell responses. We performed a placebo-controlled clinical trial evaluating the safety and immunogenicity of recombinant NY-ESO-1 protein with ISCOMATRIX adjuvant. Forty-six evaluable patients with resected NY-ESO-1-positive tumors received three doses of vaccine intramuscularly at monthly intervals. The vaccine was well tolerated. We observed high-titer antibody responses, strong delayed-type hypersensitivity reactions, and circulating CD8(+) and CD4(+) T cells specific for a broad range of NY-ESO-1 epitopes, including known and previously unknown epitopes. In an unplanned analysis, vaccinated patients appeared to have superior clinical outcomes to those treated with placebo or protein alone. The vaccine is safe and highly potent immunologically.
authors.affiliation: Ludwig Institute for Cancer Research, Melbourne 3084, Australia. ian.davis@ludwig.edu.au
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: Heather
authors.initials: H
authors.lastname: Jackson
authors.forename: Phillip
authors.initials: P
authors.lastname: Parente
authors.forename: Mark
authors.initials: M
authors.lastname: Shackleton
authors.forename: Wendie
authors.initials: W
authors.lastname: Hopkins
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Chen
authors.forename: Nektaria
authors.initials: N
authors.lastname: Dimopoulos
authors.forename: Tina
authors.initials: T
authors.lastname: Luke
authors.forename: Roger
authors.initials: R
authors.lastname: Murphy
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Scott
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Grant
authors.initials: G
authors.lastname: McArthur
authors.forename: Duncan
authors.initials: D
authors.lastname: MacGregor
authors.forename: Sue
authors.initials: S
authors.lastname: Sturrock
authors.forename: Tsin Yee
authors.initials: TY
authors.lastname: Tai
authors.forename: Simon
authors.initials: S
authors.lastname: Green
authors.forename: Andrew
authors.initials: A
authors.lastname: Cuthbertson
authors.forename: Darryl
authors.initials: D
authors.lastname: Maher
authors.forename: Lena
authors.initials: L
authors.lastname: Miloradovic
authors.forename: Susan V
authors.initials: SV
authors.lastname: Mitchell
authors.forename: Gerd
authors.initials: G
authors.lastname: Ritter
authors.forename: Achim A
authors.initials: AA
authors.lastname: Jungbluth
authors.forename: Yao-Tseng
authors.initials: YT
authors.lastname: Chen
authors.forename: Sacha
authors.initials: S
authors.lastname: Gnjatic
authors.forename: Eric W
authors.initials: EW
authors.lastname: Hoffman
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Cebon
mesh_terms: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm / Q000276:immunology*; D000951:Antigens, Neoplasm / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D000939:Epitopes; D006801:Humans; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology*; D010919:Placebos; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology*; D012503:Saponins / Q000276:immunology*; D013737:Testis / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D000276:Adjuvants, Immunologic; D000912:Antibodies, Neoplasm; D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D000939:Epitopes; D008565:Membrane Proteins; D010919:Placebos; D011994:Recombinant Proteins; D012503:Saponins