| Project/Area Number |
07807120
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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 |
Digestive surgery
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| Research Institution | Tohoku University |
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Principal Investigator |
SUZUKI Masanori School of Medicine Tohoku univ.Assi, prof., 医学部・附属病院, 助手 (70206530)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUHARA Kenji School of Medicine Tohoku univ.Assi, prof., 医学部・附属病院, 助手 (20241599)
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| Project Period (FY) |
1995 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | Bileduct Canungwy / MOC-1 / bispecific antibody / Adoptive immunotherapy / MUC-1 / bispecific抗体 / 胆嚢癌 / バイスペシフィック抗体 / 癌免疫療法 |
|---|
| Research Abstract |
For the purpose of establishing a new adoptive immunotherapy for bile duct carcinoma (BDC), we synthesized two bispecific antibodies (BsAbs), MUC1*CD3 BsAb constructed with MUSE11 (anti-MUC1 tumor antigen) and OKT-3 (anti-CD3), and MUC1*CD28 BsAb constructed with MSUE11 and 15E8 (anti-CD28) antibodies. These two BsAbs reacted well with both MUC1-positive target tumor cells and effector lymphokine-activated killer (LAK) cells. Investigation of in vitro cytotoxicity [3-(4,5-dimethylthiazo-2-yl)-2,5-diphenyltetrazolium bromide assay] revealed that the MCU1*CD3 BsAb could antigen-specifically enhance the cytotoxicity of LAK cells. Addition of the two BsAbS (MUC1*CD3 BsAb plus MUC1*CD28 BsAb) in vitro resulted in a 60% cytotoxicity, similar to that obtained with BsAb (MUC1*CD3) alone. Interleukin 12-induced LAK cells demonstrated far greater cytotoxicity (50%) than their interleukin 2-induced counterparts (LAK cells), and this was also enhanced by the BsAbs. When 2*10^7 LAK cells sensitized with both kinds of BsAbs were administered four times i.v.to BDC-grafted severe combined immunodeficient mice (tumor size 5 mm in diameter), inhibition of tumor growth was observed. Thus, BsAb-LAK therapy for control of BDC warrants clinical trials.
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