| Project/Area Number |
16591094
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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 |
Dermatology
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| Research Institution | Hamamatsu University School of Medicine |
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Principal Investigator |
YAGI Hiroaki Hamamatsu University School of Medicine, Dermatology, Assistant Professor, 医学部附属病院, 講師 (20242779)
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| Co-Investigator(Kenkyū-buntansha) |
SEO Naohiro Hamamatsu University School of Medicine, Dermatology, Instructor, 医学部, 助手 (50283354)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | melanoma / cytotoxic t cell / immunotherapy / peptide / chemokine / langerhans cell / clinical trial / ヒト / 治療 / ケモカイン受容体 |
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| Research Abstract |
Percutaneous peptide immunization (PPI) is a simple and noninvasive immunization approach to induce potent cytotoxic T lymphocyte (CTL) responses by peptide delivery via skin with the stratum corneum removed. In human skin after such barrier disruption, epidermal Langerhans cells, while functionally matured through up-regulating the expression of HLA and costimulatory molecules, were found to emigrate with reduced numbers of dendrites. CD8^+ populations binding to MHIC-peptide tetramers/pentamers and producing IFN-γ appeared in the blood after PPI with HLA class I-restricted antigenic peptides. PPI with melanoma-associated peptides reduced the lesion size and suppressed further development of tumors in four of seven advanced melanoma patients. These beneficial effects were accompanied by the generation of circulating CTLs with in vitro cytolytic activity and extensive infiltration of tetramer/pentamer-binding cells into regressing lesions. PPI elicited neither local nor systemic toxicity or autoimmunity, except for vitiligo, in melanoma patients. Therefore, PPI represents a novel therapeutic intervention for cancer in the clinical setting.
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