title: NY-ESO-1 protein formulated in ISCOMATRIX adjuvant is a potent anticancer vaccine inducing both humoral and CD8+ t-cell-mediated immunity and protection against NY-ESO-1+ tumors.
abstract: NY-ESO-1 is a 180 amino-acid human tumor antigen expressed by many different tumor types and belongs to the family of "cancer-testis" antigens. In humans, NY-ESO-1 is one of the most immunogenic tumor antigens and NY-ESO-1 peptides have been shown to induce NY-ESO-1-specific CD8(+) CTLs capable of altering the natural course of NY-ESO-1-expressing tumors in cancer patients. Here we describe the preclinical immunogenicity and efficacy of NY-ESO-1 protein formulated with the ISCOMATRIX adjuvant (NY-ESO-1 vaccine). In vitro, the NY-ESO-1 vaccine was readily taken up by human monocyte-derived dendritic cells, and on maturation, these human monocyte-derived dendritic cells efficiently cross-presented HLA-A2-restricted epitopes to NY-ESO-1-specific CD8(+) T cells. In addition, epitopes of NY-ESO-1 protein were also presented on MHC class II molecules to NY-ESO-1-specific CD4(+) T cells. The NY-ESO-1 vaccine induced strong NY-ESO-1-specific IFN-gamma and IgG2a responses in C57BL/6 mice. Furthermore, the NY-ESO-1 vaccine induced NY-ESO-1-specific CD8(+) CTLs in HLA-A2 transgenic mice that were capable of lysing human HLA-A2(+) NY-ESO-1(+) tumor cells. Finally, C57BL/6 mice, immunized with the NY-ESO-1 vaccine, were protected against challenge with a B16 melanoma cell line expressing NY-ESO-1. These data illustrate that the NY-ESO-1 vaccine represents a potent therapeutic anticancer vaccine.
authors.affiliation: Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia. Eugene_Marakovsky@csl.com.au
authors.forename: Eugene
authors.initials: E
authors.lastname: Maraskovsky
authors.forename: Sigrid
authors.initials: S
authors.lastname: Sjölander
authors.forename: Debbie P
authors.initials: DP
authors.lastname: Drane
authors.forename: Max
authors.initials: M
authors.lastname: Schnurr
authors.forename: Thuy T T
authors.initials: TT
authors.lastname: Le
authors.forename: Luis
authors.initials: L
authors.lastname: Mateo
authors.forename: Thomas
authors.initials: T
authors.lastname: Luft
authors.forename: Kelly-Anne
authors.initials: KA
authors.lastname: Masterman
authors.forename: Tsin-Yee
authors.initials: TY
authors.lastname: Tai
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Chen
authors.forename: Simon
authors.initials: S
authors.lastname: Green
authors.forename: Anders
authors.initials: A
authors.lastname: Sjölander
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Pearse
authors.forename: Francois A
authors.initials: FA
authors.lastname: Lemonnier
authors.forename: Weisan
authors.initials: W
authors.lastname: Chen
authors.forename: Jonathan
authors.initials: J
authors.lastname: Cebon
authors.forename: Andreas
authors.initials: A
authors.lastname: Suhrbier
mesh_terms: D000276:Adjuvants, Immunologic; D000818:Animals; D000951:Antigens, Neoplasm / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015704:CD4 Antigens / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019496:Cancer Vaccines; D045744:Cell Line, Tumor; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D015789:HLA-A2 Antigen / Q000737:chemistry; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000737:chemistry; D007150:Immunohistochemistry; D008546:Melanoma, Experimental; D008565:Membrane Proteins / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009000:Monocytes / Q000378:metabolism; D010455:Peptides / Q000737:chemistry; D010641:Phenotype; D010957:Plasmids / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
chemical_list: D000276:Adjuvants, Immunologic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D015704:CD4 Antigens; C104948:CTAG1B protein, human; D019496:Cancer Vaccines; D000939:Epitopes; D015789:HLA-A2 Antigen; D007074:Immunoglobulin G; D008565:Membrane Proteins; D010455:Peptides; D012333:RNA, Messenger; D011994:Recombinant Proteins