| Co-Investigator(Kenkyū-buntansha) |
YOSHINO Shigefumi Yamaguchi University, School of Medicine, Assistant Professor, 医学部, 講師 (60294633)
HINODA Yuji Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (10165128)
OKA Masaaki Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (70144946)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2003: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
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| Research Abstract |
On this project, we attempted to find clinically effective therapy against pancreatic cancer using the combination with immunotherapy and chemotherapy. For immunotherapy, we conducted two phase I trials of MUC1 peptide vaccination and personalized peptide vaccination. MUC1 mucin is glycoprotein, which is strongly recognized on the surface of pancreatic cancer cells and induces MUC1-specific cytotoxic T lymphocytes without restriction of HLA. We vaccinated 9 patients with 300, 1000, or 3000 mg of the 105 amino acid MUC1 peptide. The MUC1 vaccination was well tolerated in all patients and did not produce any side effects. In l out of 9 patients tumor markers decreased, but in the others their diseases showed progression. Secondary we applied another phase I study with personalized peptide vaccination to 10 patients with pancreatic cancer. Namely, pre-vaccinated peripheral blood mononuclear cells were screened for the reactivity in vitro to each of 14 or 16 peptide candidates in HLA-A24^+
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or -A2^+ patients, and then only the reactive peptides were vaccinated in vivo. This regimen was generally well tolerated without hematological toxicity, although inflammatory reactions at the injection site were observed in ? patients. Moreover fever, anorexia, and fatigue were observed -in 3, 1, and 1 patient, respectively. Of 10 patients who received more than 3 vaccinations and were eligible for clinical evaluation, 3 showed stable disease and 7 demonstrated progressive disease at the time of the 6th vaccination. One patient of 3 with stable disease has been alive for 30 months after the initial treatment. We demonstrated feasibility and safety of two vaccination immunotherapy, however, these therapy did not show a obvious survival benefit : On the other hand, we established a new human pancreatic cancer cell line, designated YPK-1. 50% inhibitory concentration (IC50) to YPK-1 of gemcitabine (GEM) was 0.0063 ug/ml. IC50 of cisplatin and 5-fluorouracil were 1.26 and 3.16 ug/ml, respectively. These data showed GEM may be clinically effective for pancreatic cancer among chemotherapeutic agents. In conclusion, further development of combination with personalized peptide based immunotherapy and chemotherapy using GEM for pancreatic cancer is warranted Less
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