| Project/Area Number |
19390153
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Applied pharmacology
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| Research Institution | Kagoshima University |
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Principal Investigator |
BABA Masanori Kagoshima University, 大学院・医歯学総合研究科, 教授 (70181039)
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| Co-Investigator(Kenkyū-buntansha) |
ARIMA Naomichi 鹿児島大学, 大学院・医歯学総合研究科, 教授 (30175997)
SUDA Yasuo 鹿児島大学, 大学院・理工学研究科, 教授 (70179282)
ITOU Yuji 鹿児島大学, 大学院・医歯学総合研究科, 准教授 (60223195)
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2009: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2008: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
Fiscal Year 2007: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
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| Keywords | HTLV-1 / ATL / 表面分子 / 糖鎖 / 抗体分子 / 抗体療法 |
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| Research Abstract |
Comprehensive analysis for the gene expression of human T-cell leukemia virus type 1 (HTLV-1)-infected and uninfected T cell lines by DNA microarray revealed that CD70 was a molecule highly and specifically expressed on the surface of adult T-cell leukemia (ATL) cells. Further analysis for the gene expression of glycosyltransferases by real-time PCR and high-throughput analysis of cell surface sugar chains by mass spectrometry demonstrated the existence of several ATL cell-specific sugar chains. In addition, with a newly developed fluorescent linker compound, the surface sugar chains of ATL cells were successfully immobilized on a chip. Using a human single chain Fv (scFv) phage library, a scFv specific to an ATL cell line was successfully isolated. The antigen recognized by the scFv was HLA-DR1β, which was also highly expressed on the surface of ATL cells. The scFv could induce the apoptosis of the ATL cell line at low concentrations in its dimer form. To obtain the scFv that binds to ATL cell-specific surface sugar antigens, a novel synthetic scFv library was constructed by introducing random mutations on the complementary determining regions (CDR) of a single frame antibody.
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