| Project/Area Number |
12671304
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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 |
Thoracic surgery
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| Research Institution | Shiga University of Medical Science |
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Principal Investigator |
KONTANI Keiichi Shiga University of Medical Science, the department of medicine, research associates, 医学部, 助手 (90314153)
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| Co-Investigator(Kenkyū-buntansha) |
SAWAI Satoru Shiga University of Medical Science, the department of medicine, research associates, 医学部, 助手 (60335172)
FUJINO Shozo Shiga University of Medical Science, the department of medicine, Assistant Professor, 医学部, 講師 (10209075)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | MUC1 mucin / oligopeptides / cytotoxic T lymphocytes / Dendritic cells / adoptive immunotherapy / vaccine / 肺癌 / MUC1 / 細胞傷害Tリンパ球(CTL) / 樹状細胞 |
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| Research Abstract |
1. The molecules on oligopeptides-pulsed DCs associated with MUC1 presentation
oligopeptides derived from MUC1 core protein are presented on some populations of PBMCs including DCs following uptake by the APCs. The epitope fragment reactive with SM3 is bound to both HLA class I and class II on the APCs and recognized by CTLs without an MHC-restriction.
2. Induction of MUC1-specific CTL by in vitro stimulation with MUC1 peptides
MUC1-specific CTLs can be easily induced in PBMCs from patients with lung cancer, using MUC1 peptides. Whereas, MUC1- specific CTL by mixed-lymphocyte tumor cell culture using two allogeneic MUC1-positive cancer cell lines underwent apoptotic death within 16 days. But B7-1 molecule on DCs is required for rescuing CTL from undergoing apoptotic death mediated by MUC1 mucin.
3. Clinical trial of immunotherapy targeting MUC1 mucn
Four patient with advanced lung cancer and 3 with advanced breast cancer were received injections of MUC1- specific CTLs induced in PBMCs using MUC1 peptides and dendritic cells loaded with the peptides. Clinical response was observed in 2 patients (CR 1 patient, PR 1 patient and NC 5 patients). Severe complication was not observed in all patients except for slight fever.
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