Phase I clinical trial of multiple-peptide vaccination for patients with advanced biliary tract cancer

J Transl Med. 2014 Mar 7:12:61. doi: 10.1186/1479-5876-12-61.

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.

Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN-CTR000003229).

Publication types

  • Clinical Trial, Phase I

MeSH terms

  • Adult
  • Aged
  • Biliary Tract Neoplasms / drug therapy
  • Biliary Tract Neoplasms / immunology*
  • Biliary Tract Neoplasms / pathology*
  • Cancer Vaccines / adverse effects
  • Cancer Vaccines / immunology*
  • Disease-Free Survival
  • Epitopes / immunology
  • Female
  • Humans
  • Immunity / immunology
  • Kinetics
  • Male
  • Middle Aged
  • Monitoring, Immunologic
  • Neoplasm Proteins / immunology
  • Neoplasm Staging
  • T-Lymphocytes, Cytotoxic / immunology
  • Treatment Outcome
  • Vaccination*
  • Vaccines, Subunit / adverse effects
  • Vaccines, Subunit / immunology*

Substances

  • Cancer Vaccines
  • Epitopes
  • Neoplasm Proteins
  • Vaccines, Subunit