Project/Area Number |
63570469
|
Research Category |
Grant-in-Aid for General Scientific Research (C)
|
Allocation Type | Single-year Grants |
Research Field |
Dermatology
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Research Institution | Kobe University |
Principal Investigator |
ICHIHASHI M. Kobe Univ., School of Med., Associate Prof., 医学部, 助教授 (00030867)
|
Co-Investigator(Kenkyū-buntansha) |
MISHIMA Y. Kobe Univ., School of Med., Prof., 医学部, 教授 (10073743)
|
Project Period (FY) |
1988 – 1989
|
Project Status |
Completed (Fiscal Year 1989)
|
Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1989: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1988: ¥1,300,000 (Direct Cost: ¥1,300,000)
|
Keywords | Thermal Neutron / Boron-10 / Monochromal Antibody / Melanoma Cells / 熱中性子捕捉療法 / 単クローン抗体 / ボロン-10 / 黒色腫 |
Research Abstract |
A way to selectively accumulate ^<10>B atoms in melanoma cells, independent of melanogenic activity has been studied by our research group. Our strategy for the selective killing of cancer cells is to use ^<10>B-conjugated monoclonal antibodies(MoAbs) specific for cancer- cell-associated antigens along with thermal neutron irradiation. <Methods and Results> 1. Selection of MoAb and cell line: We selected the combination of the MoAb, 753.74T and the human melanoma cell line, P22 out of many candidates, due to their highest degree of binding as assayed by cell sorter analysis. 2. Target boron concentrations on melanoma cells: If about 1 x 10^3 ^<10>B atoms are bound to one molecule of MoAb, approximately 1 x 10^9 ^<10>B atoms can be accumulated on one cancer cell. This is the theoretical number required for successful BNCT. To obtain such a high concentration of ^<10>B atom, we used the avidin-biotin method. After applying biotinated-763.74T to P22 human melanoma cells and adding ^<125>I
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labeled-avaidin, we then calculated the number of avidin molecules by measured radioactivity. The result-was 3.84 x 10^6 molecues. One avidin molecule has about 41.6 atoms of ^<10>B, so the number of ^<10>B atoms bound to one melanoma cell was approximately 1.6 x 10^8. This is smaller than our ideal number of 1 x 10^9, but we feel still reasonably close. 3. The ethal effect of thermal neutron irradiation on melanoma cells using ^<10>B-MoAbs: After applying biotinated-763.74T and ^<1O>B-avidin compound to P22 cells, suspending them in several teflon tubes (phi 1cm) of approximately 1.5 x 10^5 cells each, we irradiated them at various thermal neutron fluences. We were able tb obtained a remarkable increase in lethal effect using this system as compared with the control. We have now showed evidence that we can accumulate ^<10>B-MoAbs on human melanoma cells using the avidin-biotin method. Next we would like to cure human melanoma-bearing nude mice by this method and eventually cure human patients suffering from various kinds of cancer. Less
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