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2007Sato Yuji; Fujiwara Toshiyoshi; Mine Takashi; Shomura Hiroki; Homma Shigenori; Maeda Yoshiaki; Tokunaga Naoyuki; Ikeda Yoshihiro; Ishihara Yuki; Yamada Akira; Tanaka Noriaki; Itoh Kyogo; Harada Mamoru; Todo Satoru
Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients.
Cancer science 2007;98(7):1113-9.
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.

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