title: Phase II Study of Personalized Peptide Vaccination with Both a Hepatitis C Virus-Derived Peptide and Peptides from Tumor-Associated Antigens for the Treatment of HCV-Positive Advanced Hepatocellular Carcinoma Patients.
abstract: Objective. To evaluate safety and immune responses of personalized peptide vaccination (PPV) for hepatitis C virus- (HCV-) positive advanced hepatocellular carcinoma (HCC). Patients and Methods. Patients diagnosed with HCV-positive advanced HCC were eligible for this study. A maximum of four HLA-matched peptides were selected based on the preexisting IgG responses specific to 32 different peptides, which consisted of a single HCV-derived peptide at core protein positions 35-44 (C-35) and 31 peptides derived from 15 different tumor-associated antigens (TAAs), followed by subcutaneous administration once per week for 8 weeks. Peptide-specific cytotoxic T lymphocyte (CTL) and IgG responses were measured before and after vaccination. Results. Forty-two patients were enrolled. Grade 3 injection site skin reaction was observed in 2 patients, but no other PPV-related severe adverse events were noted. Peptide-specific CTL responses before vaccination were observed in only 3 of 42 patients, but they became detectable in 23 of 36 patients tested after vaccination. Peptide-specific IgG responses were also boosted in 19 of 36 patients. Peptide-specific IgG1 responses to both C-35 and TAA-derived peptides could be potentially prognostic for overall survival. Conclusion. Further clinical study of PPV would be warranted for HCV-positive advanced HCC, based on the safety and strong immune induction.
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume 839-0863, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yutani
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka 589-8511, Japan.
authors.forename: Kazuomi
authors.initials: K
authors.lastname: Ueshima
authors.affiliation: Department of Digestive, Rheumatism and Collagen Internal Medicine, Fukushima Prefectural Medical College, Fukushima 960-1295, Japan.
authors.forename: Kazumichi
authors.initials: K
authors.lastname: Abe
authors.affiliation: Department of Medical Oncology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ishiguro
authors.affiliation: Department of Gastroenterology, Showa University School of Medicine, Tokyo 142-8555, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Eguchi
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume 839-0863, Japan.
authors.forename: Satoko
authors.initials: S
authors.lastname: Matsueda
authors.affiliation: Department of Immunology, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Komatsu
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume 839-0863, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Shichijo
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume 830-0011, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Yamada
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume 839-0863, Japan.
authors.forename: Kyogo
authors.initials: K
authors.lastname: Itoh
authors.affiliation: Cancer Vaccine Center, Kurume University, Kurume 839-0863, Japan ; Department of Immunology, Kurume University School of Medicine, Kurume 830-0011, Japan.
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Sasada
authors.affiliation: Department of Gastroenterology and Hepatology, Kinki University Faculty of Medicine, Osaka 589-8511, Japan.
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Kudo
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume 830-0011, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Noguchi
mesh_terms: D000328:Adult; D000368:Aged; D000951:Antigens, Neoplasm / Q000008:administration & dosage / Q000737:chemistry / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology; D019496:Cancer Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000628:therapy* / Q000821:virology*; D005260:Female; D016174:Hepacivirus / Q000737:chemistry* / Q000276:immunology; D006526:Hepatitis C / Q000175:diagnosis; D006801:Humans; D007115:Immunization Schedule; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000628:therapy / Q000821:virology; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D019496:Cancer Vaccines; D007074:Immunoglobulin G; D022223:Vaccines, Subunit