title: Immunological features of T cells induced by human telomerase reverse transcriptase-derived peptides in patients with hepatocellular carcinoma.
abstract: Human telomerase reverse transcriptase (hTERT) is a catalytic enzyme required for telomere elongation. In this study, we investigated the safety and immunogenicity of an hTERT-derived peptide (hTERT461) as a vaccine and characterized the hTERT-specific T cell responses induced. Fourteen hepatocellular carcinoma (HCC) patients were enrolled in the study. The hTERT-derived peptide was emulsified in incomplete Freund's adjuvant and administered via subcutaneous immunization three times biweekly. The maximum toxicity observed was grade 2 according to the common terminology criteria and mainly consisted of skin reactions at the site of vaccination. The vaccination induced hTERT-specific immunity in 71.4% of patients and 57.1% of patients administered with hTERT461 peptide-specific T cells could prevent HCC recurrence after vaccination. In phenotypic analysis, the post-vaccinated increase in hTERT-specific T cells was due to an increase in cells with the effector memory phenotype, with the potential to produce multiple cytokines. Seven hTERT-specific T cell receptors were obtained from the vaccinated patients, showing their cytotoxic activities to hTERT-derived peptide-bearing cells. In conclusion, the safety and effects of immune boosting by hTERT461 peptide have shown the potential of the peptide to provide clinical benefits in HCC patients.
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Eishiro
authors.initials: E
authors.lastname: Mizukoshi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Nakagawa
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kitahara
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamashita
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Arai
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Sunagozaka
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Fushimi
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Kobayashi
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kishi
authors.affiliation: Department of Immunology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Muraguchi
authors.affiliation: Department of Gastroenterology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan. Electronic address: skaneko@m-kanazawa.jp.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Kaneko
mesh_terms: D000368:Aged; D019496:Cancer Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology; D045744:Cell Line, Tumor; D005260:Female; D059871:HLA-A24 Antigen / Q000276:immunology; D006801:Humans; D016130:Immunophenotyping; D020014:K562 Cells; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects / Q000276:immunology; D019098:Telomerase / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; C438506:HLA-A*24:02 antigen; D059871:HLA-A24 Antigen; D010446:Peptide Fragments; C509186:TERT protein, human; D019098:Telomerase
keywords: Cancer; Cytotoxic T cell; Epitope; Immunotherapy; T cell receptor