1997 Fiscal Year Final Research Report Summary
Specific cancer immunotherapy using tumor-rejection antigens of MAGE.
| Project/Area Number |
08557074
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
General surgery
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
TSUYOSHI Akiyoshi MEDICAL INSTITUTE OF BIOREGULATION,KYUSHU UNIVERSITY,PROFESSOR, 生体防御医学研究所, 教授 (70038660)
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| Co-Investigator(Kenkyū-buntansha) |
YASUMOTO Masazumi BIOTECHNOLOGY RESEARCH LABORATORIES,TAKARA SHUZO CO., LTD.RESEARCHER, バイオ研究所, 研究員
TAKESAKO Kazutoh BIOTECHNOLOGY RESEARCH LABORATORIES,TAKARA SHUZO CO., LTD.VISE DIRECTOR, バイオ研究所, 副室長
TOH Yasushi CLINICAL RESEARCH INSTITUTE,NATIONAL KYUSHU CANCER CENTER,DIVISION OF HEAD, 臨床研究部, 室長 (20217459)
YAMAGATA Motoyuki MEDICAL INSTITUTE OF BIOREGULATION,KYUSHU UNIVERSITY,LECTURER, 生体防御医学研究所, 助手 (90294975)
HARAGUCHI Masaru MEDICAL INSTITUTE OF BIOREGULATION,KYUSHU UNIVERSITY,ASSISTANT PROFESSOR, 生体防御医学研究所, 講師 (40228531)
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| Project Period (FY) |
1996 – 1997
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| Keywords | tumor-rejection antigen / specific cancer immunotherapy / MAGE / antigenic peptide / cytotoxic Tlymphocyte / dendritic cell / cancer vaccine therapy |
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| Research Abstract |
1. The expression of MAGE-1, -2, and-3 genes was relatively high in gastrointestinal carcinomas (40% in gastric carcinoma, 60% in esophageal carcinomas, and 60% in hepatocellular carcinomas). Eighty to 90% of these carcinomas expressed at least one of MAGE-1 to-12genes.
2. Using our newly developed, simplified method, MAGE peptide-specificcytotoxic T lymphocytes (CTL) that killed MAGE expressing tumor cells, as well as target cells pulsed with the peptide, could be induced from peripheral blood mononuclear cells (PBMC) of either healthy donors or cancer patients.
3. Because HLA-A24 is the most common allele in Japanese, MAGE-encoded peptides with a high binding affinity to HLA-A24 were defined based on the screening of sequences for the presence of MHC binding motifs. The immunogenicity of these pepitides was then tested by primary in vitro CTL induction using our simplified method. As the results, HLA-A24 restricted potential MAGE-1 and-3 peptides, IMPKAGLLI and NYKHCFPEI,have been identified.
4. Clinical trials using MAGE Peptides have been approved by ethics commitee of this institute. Therefore, patients with advanced gastrointestinal carcinoma have been treated with autologous dendritic cells pulsed with MAGE peptide as cancer vaccine. Following the treatment, one patient with advanced gastric carcinoma developed inflammatory change at tumor site of abdominal wall and specific CTL could be induced from PBMC of the patient. In a patient with recurrent carcinoma of the esophagus, metastatic tumor of cervial region has been regressed after two administration of the cancer vaccine. These results may suggest the effectiveness of this type of vaccine therapy using MAGE peptides.
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