| Project/Area Number |
09671815
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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 |
Ophthalmology
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| Research Institution | KEIO University |
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Principal Investigator |
OHTAKE Yuichiro School of Medicine, KEIO University Instructor, 医学部, 助手 (30233159)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Nobuyoshi School of Medicine,KEIO University Professor, 医学部, 教授 (50162706)
TAKAYANAGI Atsushi School of Medicine,KEIO University Instructor, 医学部, 助手 (80245464)
MASHIMA Yukihiro School of Medicine,KEIO University Associate Professor, 医学部, 助教授 (40157186)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1997: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | melanoma / intra ocular tumor / gene therapy / monoclonal antibody / artificial antibody / immunogene |
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| Research Abstract |
The Fab fragment of monoclonal antibody B4G7 against human epidermal growth factor (EGF) receptor was conjugated with a cationic poly-L-lysine and the resulting conjugate was further complexed with reporter genes or therapeutic genes. This Fab/DNA complex was designated as "Fab immunogene". The Fab immunogene transfer in vitro was mediated through the EGF receptors in two melanoma cell lines as measured for the expression of β-galactosidase (β-Gal) gene. The frequency of β-Gal gene expressing cells was approximately 1%. The induction of suicide effects after Fab immunogene transfer of herpes simplex virus thymidine kinase (TK) or Escherichia coli cytosine deaminase (CD) gene was quite remarkable, inhibiting the growth of melanoma cells for over 7 days in the presence of ganciclovir or 5-fluorocytosine (5-FC) .
Similarly, when melanoma cells treated in vitro with the Fab immunogene carrying TK or CD were transplanted into the back of nude mouse, subsequent systemic administration of GCV or 5-FC effectively suppressed the growth of tumors, indicating the in vivo suicide effects.
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