title: Vaccination with peptides derived from cancer-testis antigens in combination with CpG-7909 elicits strong specific CD8+ T cell response in patients with metastatic esophageal squamous cell carcinoma.
abstract: Potent helper action is necessary for peptide-based vaccines to efficiently induce antitumor immune responses against advanced cancer. A phase I trial for advanced esophageal squamous cell carcinoma was carried out for patients with HLA-A*2402 using epitope peptides derived from novel cancer-testis antigens, LY6K and TTK, in combination with CpG-7909 (NCT00669292). This study investigated the feasibility and the toxicity as well as induction of tumor antigen-specific immune responses. Nine patients were vaccinated on days 1, 8, 15, and 22 of each 28-day treatment cycle with peptide LY6K-177, peptide TTK-567, and CpG-7909 (level-1; 0, level-2; 0.02, level-3; 0.1 mg/kg) and all were tolerated by this treatment. LY6K-specific T cell responses in PBMCs were detected in two of the three patients in each level. In particular, two patients in level-2/3 showed potent LY6K-specific T cell responses. In contrast, only two patients in level-2/3 showed TTK-567-specific T cell responses. The frequency of LY6K-177 or TTK-567-specific CD8+ T cells increased in patients in level-2/3 (with CpG). The vaccination with peptides and CpG-7909 increased and activated both plasmacytoid dendritic cells and natural killer cells, and increased the serum level of α-interferon. There were no complete response (CR) and partial response (PR), however, one of three patients in level-1, and four of six patients in level-2/3 showed stable disease (SD). In conclusion, vaccination with LY6K-177 and TTK-567 in combination with CpG-7909 successfully elicited antigen-specific CD8+ T cell responses and enhanced the innate immunity of patients with advanced esophageal squamous cell carcinoma. This vaccine protocol is therefore recommended to undergo further phase II trials.
authors.affiliation: Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Iwahashi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Katsuda
authors.forename: Mikihito
authors.initials: M
authors.lastname: Nakamori
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakamura
authors.forename: Teiji
authors.initials: T
authors.lastname: Naka
authors.forename: Toshiyasu
authors.initials: T
authors.lastname: Ojima
authors.forename: Takeshi
authors.initials: T
authors.lastname: Iida
authors.forename: Hiroki
authors.initials: H
authors.lastname: Yamaue
mesh_terms: D000368:Aged; D000950:Antigens, Ly / Q000276:immunology / Q000627:therapeutic use; D000951:Antigens, Neoplasm / Q000276:immunology / Q000627:therapeutic use*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D019496:Cancer Vaccines / Q000276:immunology / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000276:immunology*; D018797:Cell Cycle Proteins / Q000276:immunology / Q000627:therapeutic use; D002469:Cell Separation; D016207:Cytokines / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D004938:Esophageal Neoplasms / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D058851:GPI-Linked Proteins / Q000276:immunology / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009838:Oligodeoxyribonucleotides / Q000276:immunology / Q000627:therapeutic use*; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases; D014611:Vaccination / Q000379:methods; D022223:Vaccines, Subunit / Q000276:immunology / Q000627:therapeutic use
chemical_list: D000950:Antigens, Ly; D000951:Antigens, Neoplasm; D019496:Cancer Vaccines; D018797:Cell Cycle Proteins; D016207:Cytokines; D058851:GPI-Linked Proteins; C525725:LY6K protein, human; D009838:Oligodeoxyribonucleotides; C483020:ProMune; D022223:Vaccines, Subunit; D011505:Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; C075840:TTK protein, human