| Project/Area Number |
16500327
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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 |
Medical systems
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| Research Institution | Fukuoka University |
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Principal Investigator |
KUROKI Motomu Fukuoka University, School of Medicine, Assistant Professor, 医学部, 講師 (10131822)
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| Co-Investigator(Kenkyū-buntansha) |
SHIBAGUCHI Hirotomo Fukuoka University, School of Medicine, Lecturer, 医学部, 助手 (60295061)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
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| Keywords | monoclonal antibody / ultrasound / sonosensitizer / Ep-CAM / cancer |
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| Research Abstract |
(1)Effect of DCPH-P on ultrasound treatment of tumor cells.
When gastric tumor cells were exposed to ultrasound or halogen light in the presence of DCPH-P in vitro, cytotoxic activities were observed by ultrasound but not by halogen light, indicating that DCPH-P is a new sono-sensitizer that reveals little sensitivity to light. Moreover, the combination of DCPH-P and ultrasound exhibited anti-tumor effects against gastric tumor cells in a mouse xenograft model.
(2)Preparation of immuno-conjugates of DCPH-P.
Conjugation of DCPH-P to monoclonal antibodies (MAbs) was assessed using mouse MAb for CEA in the presence of EDC, a water-soluble carbodiimide, and N-hydroxysulfosuccinimide. The resulting conjugates showed a significant augmented effect on the cytotoxic activity against CEA-expressing tumor cells by ultrasound both in vitro and in a mouse xenograft model.
(3)Preparation of human MAb against Ep-CAM (MK-1).
Recombinant Ep-CAM was injected into KM mice, which contain human genes for immunoglobulin. Spleen cells of the mice were hybridized with mouse myeloma cells P3-U1. From about 3,000 hybridoma clones, 40 clones reactive with Ep-CAM were obtained. Two IgG4 MAbs, purified after production in nude mice, were specifically reactive with Ep-CAM-expressing tumor cells. To obtain a small molecule single chain antibody, V-region genes of H and L chains were cloned, and combined and expressed in E.coli. The resulting single chain antibody will be conjugated with DCPH-P for sonodynamic treatment of Ep-CAM-expressing tumor cells.
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