Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients

Cancer Sci. 2007 Jul;98(7):1113-9. doi: 10.1111/j.1349-7006.2007.00498.x. Epub 2007 Apr 23.


The aim of the present study was to investigate the safety and immunological responses of personalized peptide vaccination in combination with oral administration of a 5-fluorouracil derivative (TS-1) in advanced gastric or colorectal carcinoma patients. Eleven patients (four with gastric cancer and seven with colorectal cancer) who failed to improve by prior TS-1-based chemotherapies were enrolled in this study. Peptides to be administered to patients were determined based on the presence of peptide-specific cytotoxic T lymphocyte (CTL) precursors in peripheral blood mononuclear cells and peptide-specific IgG in the plasma of cancer patients. Patients were vaccinated with peptides (a maximum of four) biweekly in combination with or without three different doses of TS-1 (20, 40 and 80 mg/m(2)/day). Although grade 3 toxicity, including anemia (one patient) and neutropenia (one patient) were observed, the combination therapy was generally well tolerated. An increase in peptide-specific IgG after the sixth vaccination was observed in the vast majority of patients irrespective of the dose of TS-1 used. In contrast, an increase in peptide-specific interferon-gamma production by CTL was most evident in patients who were administered the highest dose of TS-1. Furthermore, in the patients who received 80 mg/m(2)/day TS-1, CTL-mediated cytotoxicity against cancer cells was maintained at the prevaccination level. These results indicate that administration of the standard dose (80 mg/m(2)/day) of TS-1 in combination with a personalized peptide vaccination does not necessarily impede immunological responses in cancer patients, and could actually maintain or augment them.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Cancer Vaccines / therapeutic use*
  • Cell Survival
  • Colorectal Neoplasms / immunology
  • Colorectal Neoplasms / pathology
  • Colorectal Neoplasms / therapy*
  • Combined Modality Therapy
  • Female
  • Fluorouracil / analogs & derivatives
  • Fluorouracil / therapeutic use*
  • HLA-A Antigens / immunology
  • HLA-A2 Antigen / immunology
  • HLA-A24 Antigen
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Middle Aged
  • Stomach Neoplasms / immunology
  • Stomach Neoplasms / pathology
  • Stomach Neoplasms / therapy*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology


  • Cancer Vaccines
  • HLA-A Antigens
  • HLA-A2 Antigen
  • HLA-A24 Antigen
  • Interferon-gamma
  • Fluorouracil