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/m2/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-γ 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/m2/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/m2/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.
| Original language | English |
|---|---|
| Pages (from-to) | 1113-1119 |
| Number of pages | 7 |
| Journal | Cancer Science |
| Volume | 98 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2007 |
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ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients. / Sato, 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.
In: Cancer Science, Vol. 98, No. 7, 07.2007, p. 1113-1119.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Immunological evaluation of personalized peptide vaccination in combination with a 5-fluorouracil derivative (TS-1) for advanced gastric or colorectal carcinoma patients
AU - Sato, Yuji
AU - Fujiwara, Toshiyoshi
AU - Mine, Takashi
AU - Shomura, Hiroki
AU - Homma, Shigenori
AU - Maeda, Yoshiaki
AU - Tokunaga, Naoyuki
AU - Ikeda, Yoshihiro
AU - Ishihara, Yuki
AU - Yamada, Akira
AU - Tanaka, Noriaki
AU - Itoh, Kyogo
AU - Harada, Mamoru
AU - Todo, Satoru
PY - 2007/7
Y1 - 2007/7
N2 - 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/m2/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-γ 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/m2/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/m2/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.
AB - 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/m2/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-γ 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/m2/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/m2/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.
UR - http://www.scopus.com/inward/record.url?scp=34249879033&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249879033&partnerID=8YFLogxK
U2 - 10.1111/j.1349-7006.2007.00498.x
DO - 10.1111/j.1349-7006.2007.00498.x
M3 - Article
C2 - 17459063
AN - SCOPUS:34249879033
VL - 98
SP - 1113
EP - 1119
JO - Cancer Science
JF - Cancer Science
SN - 1347-9032
IS - 7
ER -