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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.
Austin Authors: Maraskovsky, Eugene;Sjölander, Sigrid;Drane, Debbie P;Schnurr, Max;Le, Thuy T T;Mateo, Luis;Luft, Thomas;Masterman, Kelly-Anne;Tai, Tsin-Yee;Chen, Qiyuan;Green, Simon;Sjölander, Anders;Pearse, Martin J;Lemonnier, Francois A;Chen, Weisan;Cebon, Jonathan S ;Suhrbier, Andreas
Affiliation: Ludwig Institute for Cancer Research, Austin and Repatriation Medical Centre, Melbourne, Victoria, Australia
Issue Date: 15-Apr-2004
Publication information: Clinical Cancer Research; 10(8): 2879-90
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.
Gov't Doc #: 15102697
Type: Journal Article
Subjects: Adjuvants, Immunologic
Antigens, CD4.biosynthesis
Antigens, Neoplasm.chemistry
Antineoplastic Agents.pharmacology
CD8-Positive T-Lymphocytes.immunology.metabolism
Cancer Vaccines
Cell Line, Tumor
Disease Progression
Dose-Response Relationship, Drug
Enzyme-Linked Immunosorbent Assay
Escherichia coli.metabolism
HLA-A2 Antigen.chemistry
Immunity, Cellular
Immunoglobulin G.chemistry
Melanoma, Experimental
Membrane Proteins.chemistry
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
RNA, Messenger.metabolism
Recombinant Proteins.chemistry
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Appears in Collections:Journal articles

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