2002 Fiscal Year Final Research Report Summary
Development of cancer vaccine therapy targeting CEA and the analysis of its immunologicai responses
| Project/Area Number |
12671252
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Digestive surgery
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| Research Institution | Wakayama medical school |
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Principal Investigator |
UCHIYAMA Kazuhisa Wakayama Medical University Second Department of Surgery Associate Professor, 医学部, 助教授 (80232867)
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| Co-Investigator(Kenkyū-buntansha) |
TANI Masaji Wakayama Medical University Second Department of Surgery Assistant Professor, 医学部, 助手 (60236677)
IWAHASHI Makoto Wakayama Medical University Second Department of Surgery Assistant Professor, 医学部, 講師 (70244738)
YAMAUE Hiroki Wakayama Medical University Second Department of Surgery Professor, 医学部, 教授 (20191190)
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| Project Period (FY) |
2000 – 2002
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| Keywords | CEA / CTL / DC / ELISPOT |
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| Research Abstract |
Carcinoembryonic antigen (CEA) is strongly expressed in vast majority of gastrointestinal malignancies. Recently several epitope peptides derived from CEA were identified. It was already clarified HLA-A24 restricted peptide CEA652[9] (TYACFVSNL) was capable of eliciting specific CTL which could lyse tumor cells expressing HLA-A24 and CEA. HLA-A24 is the most applicable MHC class I allele in Japanese. In this pilot study, we used peptide pulsed dendritic cells (DCs) generated from peripheral blood mononuclear cells supplemented with GM-CSF and IL-4. Eight patients with advanced CEA expressing gastrointestinal malignancies received every 2 or 3 weeks subcutaneous vaccination. Changes in CTL reactivity after vaccinations were assessed by enzyme-linked immunospot (ELISPOT) assay and their capacity to elicit anti-tumor CTL in vitro. Three of six patients developed their CTL reactivity after vaccinations. Two of six patients responded in ELISPOT assay. DTH reaction was observed in one of eight patients at the injected site. Skin biopsy at the injected site demonstrated infiltration of lymphocytes. However no major tumor regressions were observed. No significant toxic adverse effects were observed except mild diarrhea in one case after three times vaccination. In conclusion, our results demonstrated that peptide pulsed DCs injected subcutaneously was safe and could develop peptide specific CTL activity in cancer pattante.
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