title: Immunodominant CD4+ responses identified in a patient vaccinated with full-length NY-ESO-1 formulated with ISCOMATRIX adjuvant.
abstract: There is increasing evidence showing the involvement of CD4(+) T cells in initiating and maintaining antitumor immune responses. NY-ESO-1 is expressed by various tumors but not normal tissues except testis. We conducted a cancer clinical trial by using full-length NY-ESO-1 protein formulated with ISCOMATRIX adjuvant and injected into patients intramuscularly. Autologous dendritic cells pulsed with NY-ESO-1 ISCOMATRIX in combination with overlapping synthetic peptides were used to identify immunodominant T cells from a vaccinated patient. We show here the identification and characterization of two novel CD4(+) T cell epitopes. T cells specific to these epitopes not only recognized autologous dendritic cells loaded with NY-ESO-1 but also NY-ESO-1-expressing tumor cell lines treated with IFN-gamma. One of the two responses identified was greater than the previously identified immunodominant HLA-DP4-restricted response and correlated with NY-ESO-1-specific CD8(+) T cell induction after vaccination. This T cell response was vaccinated in most patients who expressed HLA-DR2. This study has systematically surveyed patients vaccinated with full-length tumor antigen for a vaccinated CD4 helper T cell response.
authors.affiliation: Ludwig Institute for Cancer Research, Austin Health, 145-163 Studley Road, Heidelberg, Victoria 3084, Australia.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Chen
authors.forename: Heather
authors.initials: H
authors.lastname: Jackson
authors.forename: Phillip
authors.initials: P
authors.lastname: Parente
authors.forename: Tina
authors.initials: T
authors.lastname: Luke
authors.forename: Mark
authors.initials: M
authors.lastname: Rizkalla
authors.forename: Tsin Yee
authors.initials: TY
authors.lastname: Tai
authors.forename: He-Cheng
authors.initials: HC
authors.lastname: Zhu
authors.forename: Nicole A
authors.initials: NA
authors.lastname: Mifsud
authors.forename: Nektaria
authors.initials: N
authors.lastname: Dimopoulos
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Masterman
authors.forename: Wendie
authors.initials: W
authors.lastname: Hopkins
authors.forename: Heather
authors.initials: H
authors.lastname: Goldie
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Simon
authors.initials: S
authors.lastname: Green
authors.forename: Lena
authors.initials: L
authors.lastname: Miloradovic
authors.forename: James
authors.initials: J
authors.lastname: McCluskey
authors.forename: Lloyd J
authors.initials: LJ
authors.lastname: Old
authors.forename: Ian D
authors.initials: ID
authors.lastname: Davis
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000951:Antigens, Neoplasm / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D000939:Epitopes / Q000737:chemistry / Q000276:immunology; D006801:Humans; D008213:Lymphocyte Activation; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D008565:Membrane Proteins / Q000276:immunology*; D008969:Molecular Sequence Data; D013737:Testis / Q000276:immunology; D014614:Vaccines, Synthetic / Q000276:immunology*
chemical_list: D000951:Antigens, Neoplasm; C104948:CTAG1B protein, human; D000939:Epitopes; D008565:Membrane Proteins; D014614:Vaccines, Synthetic