title: Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer.
abstract: BACKGROUND
  The prognosis of patients with advanced biliary tract cancer (BTC) is extremely poor and only a few standard treatments are available for this condition. We performed a phase I trial to investigate the safety, immune response and anti-tumor effect of vaccination with three peptides derived from cancer-testis antigens.
  
  
  METHODS
  This study was conducted as a phase I trial. Nine patients with advanced BTC who had unresectable tumors and were refractory to standard chemotherapy were enrolled. Three HLA-A*2402 restricted epitope peptides-cell division cycle associated 1 (CDCA1), cadherin 3 (CDH3) and kinesin family member 20A (KIF20A)-were administered subcutaneously, and the adverse events and immune response were assessed. The clinical effects observed were the tumor response, progression-free survival (PFS) and overall survival (OS).
  
  
  RESULTS
  The three-peptide vaccination was well-tolerated up to a dose of 3 mg per peptide (9 mg total). No grade 3 or 4 adverse events were observed after vaccination. Peptide-specific T cell immune responses were observed in all patients and stable disease was observed in 5 of 9 patients. The median PFS and OS were 3.4 and 9.7 months. The Grade 2 injection site reaction and continuous vaccination after PD judgment appeared to be prognostic of OS.
  
  
  CONCLUSIONS
  Multiple-peptide vaccination was well tolerated and induced peptide-specific T-cell responses.
  
  
  BACKGROUND
  This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003229).
authors.affiliation: Department of Gastroenterological Surgery, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. aruga.atsushi@twmu.ac.jp.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Aruga
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Takeshita
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kotera
authors.forename: Ryuji
authors.initials: R
authors.lastname: Okuyama
authors.forename: Norimasa
authors.initials: N
authors.lastname: Matsushita
authors.forename: Takehiro
authors.initials: T
authors.lastname: Ohta
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000328:Adult; D000368:Aged; D001661:Biliary Tract Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D019496:Cancer Vaccines / Q000009:adverse effects / Q000276:immunology*; D018572:Disease-Free Survival; D000939:Epitopes / Q000276:immunology; D005260:Female; D006801:Humans; D007109:Immunity / Q000276:immunology; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D015166:Monitoring, Immunologic; D009363:Neoplasm Proteins / Q000276:immunology; D009367:Neoplasm Staging; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D016896:Treatment Outcome; D014611:Vaccination; D022223:Vaccines, Subunit / Q000009:adverse effects / Q000276:immunology*
chemical_list: D019496:Cancer Vaccines; D000939:Epitopes; D009363:Neoplasm Proteins; D022223:Vaccines, Subunit