title: Immunization with analog peptide in combination with CpG and montanide expands tumor antigen-specific CD8+ T cells in melanoma patients.
abstract: Analog peptides represent a promising tool to further optimize peptide-based vaccines in promoting the expansion of tumor antigen-specific cytotoxic T lymphocytes. Here, we report the results of a pilot trial designed to study the immunogenicity of the analog peptide NY-ESO-1 157-165V in combination with CpG 7909/PF3512676 and Montanide ISA 720 in patients with stage III/IV NY-ESO-1-expressing melanoma. Eight patients were immunized either with Montanide and CpG (arm 1, 3 patients); Montanide and peptide NY-ESO-1 157-165V (arm 2, 2 patients); or with Montanide, CpG, and peptide NY-ESO-1 157-165V (arm 3, 3 patients). Only the 3 patients immunized with Montanide, CpG, and peptide NY-ESO-1 157-165V in arm 3 developed a rapid increase of effector-memory NY-ESO-1-specific CD8+ T cells, detectable ex vivo. The majority of these cells exhibited an intermediate/late-stage differentiated phenotype (CD28-). Our study further demonstrated that our vaccine approach stimulated spontaneous tumor-reactive NY-ESO-1-specific CD8+ T cells in 2 patients with advanced disease, but failed to prime tumor-reactive NY-ESO-1-specific T cells in 1 patient with no spontaneously tumor-induced CD8+ T-cell responses to NY-ESO-1. Collectively, our data support the capability of the analog peptide NY-ESO-1 157-165V in combination with CpG and Montanide to promote the expansion of NY-ESO-1-specific CD8+ T cells in patients with advanced cancer. They also suggest that the presence of tumor-induced NY-ESO-1-specific T cells of well-defined clonotypes is critical for the expansion of tumor-reactive NY-ESO-1-specific CD8+ T cells after peptide-based vaccine strategies.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213-2582, USA.
authors.forename: Julien
authors.initials: J
authors.lastname: Fourcade
authors.forename: Pavol
authors.initials: P
authors.lastname: Kudela
authors.forename: Pedro A
authors.initials: PA
authors.lastname: Andrade Filho
authors.forename: Bratislav
authors.initials: B
authors.lastname: Janjic
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Land
authors.forename: Cindy
authors.initials: C
authors.lastname: Sander
authors.forename: Arthur
authors.initials: A
authors.lastname: Krieg
authors.forename: Albert
authors.initials: A
authors.lastname: Donnenberg
authors.forename: Hongmei
authors.initials: H
authors.lastname: Shen
authors.forename: John M
authors.initials: JM
authors.lastname: Kirkwood
authors.forename: Hassane M
authors.initials: HM
authors.lastname: Zarour
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007114:Immunization; D008297:Male; D008353:Mannitol / Q000031:analogs & derivatives / Q000627:therapeutic use; D008545:Melanoma / Q000276:immunology* / Q000628:therapy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000276:immunology / Q000627:therapeutic use*; D009829:Oleic Acids / Q000627:therapeutic use; D009838:Oligodeoxyribonucleotides / Q000627:therapeutic use; D010446:Peptide Fragments / Q000276:immunology / Q000627:therapeutic use*; D010865:Pilot Projects; D012878:Skin Neoplasms / Q000276:immunology* / Q000628:therapy; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D019496:Cancer Vaccines; D009363:Neoplasm Proteins; D009829:Oleic Acids; D009838:Oligodeoxyribonucleotides; D010446:Peptide Fragments; C483020:ProMune; C504237:peptide NY-ESO-1 157-165; C001681:mannide monooleate; D008353:Mannitol
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