title: Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients.
abstract: 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.
authors: Department of General Surgery, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors: Yuji
authors: Y
authors: Sato
authors: Toshiyoshi
authors: T
authors: Fujiwara
authors: Takashi
authors: T
authors: Mine
authors: Hiroki
authors: H
authors: Shomura
authors: Shigenori
authors: S
authors: Homma
authors: Yoshiaki
authors: Y
authors: Maeda
authors: Naoyuki
authors: N
authors: Tokunaga
authors: Yoshihiro
authors: Y
authors: Ikeda
authors: Yuki
authors: Y
authors: Ishihara
authors: Akira
authors: A
authors: Yamada
authors: Noriaki
authors: N
authors: Tanaka
authors: Kyogo
authors: K
authors: Itoh
authors: Mamoru
authors: M
authors: Harada
authors: Satoru
authors: S
authors: Todo
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D019496:Cancer Vaccines / Q000627:therapeutic use*; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000031:analogs & derivatives / Q000627:therapeutic use*; D015234:HLA-A Antigens / Q000276:immunology; D015789:HLA-A2 Antigen / Q000276:immunology; D059871:HLA-A24 Antigen; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013274:Stomach Neoplasms / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
chemical_list: D019496:Cancer Vaccines; D015234:HLA-A Antigens; D015789:HLA-A2 Antigen; D059871:HLA-A24 Antigen; D007371:Interferon-gamma; D005472:Fluorouracil