| Project/Area Number |
08671350
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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 |
General surgery
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| Research Institution | GIFU UNIVERSITY |
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Principal Investigator |
KATO Motohisa GIFU UNIVERSITY SCHOOL OF MEDICINE ASSISTANT PROFESSOR, 医学部・附属病院, 助手 (20224545)
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| Co-Investigator(Kenkyū-buntansha) |
UMEMOTO Takao GIFU UNIVERSITY SCHOOL OF MEDICINE LECTURER, 医学部・附属病院, 講師 (40223614)
MIYA Kiichi GIFU UNIVERSITY SCHOOL OF MEDICINE LECTURER, 医学部・附属病院, 講師 (10190729)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | interleukin-12 / LAK / CTL / dendritic cell / 養子免疫療法 / Interleukin-12 / IL-12 / SCIDマウス / IFNγ |
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| Research Abstract |
(1) Anti-tumor effect of systemically administrated human IL-12 was investigated using SCID mice. It is suggested that tumor-infiltrating lymphocytes (TIL) have anti-tumor effect against engrafted human lung cancer tissue and that peripheral blood mononuclear cells also do against gastric cancer cell line engrafted intraperitoneally.
(2) Optimal combined concentration of IL-2 and IL-12 in induction of LAK cells was investigated by measuring LAX activities. LAX activities was elevated when more than 100U/ml of IL-2 and LOU/ml of IL-12 was added into culture media.
(3) We investigated how to induce CTL using Dcs. The way using GM-CSF+IL-4 was better than stepwise centrifugation method using metrizamide about separation of DCs. DCs pulsed with cancer cells induced higher cytotoxicity upon autologous cancer cells than LAK cells and effector cells stimulated with cancer cells alone. However, their cytotoxicity were almost all less than 20% and was not satisfactory. Anti-CD3 increased the number of effector cells less than expected.
(4) Clinical cases of adoptive immunotherapy : 1) LAK cells induced with IL-2+IL- 12 .were administered through hepatic arterial port against liver metastasis of colon cancer three times, but they had no effect. 2) Autologous cancer cells were taken from pleural effusion and were used for pulse of DCs. DC killer cells were induced using DCs prepared with IL-4+GM-CSF.The DC killer cells administered intravenously into a breast cancer patient with lung metastasis and an esophageal cancer patient with mediastinal lymph node and skin metastasis. However, cancer progressed in the both cases, although tumor marker level in serum declined and a part of skin metastases disappeared.
In order to aim better clinical effect, we are trying to induce DC-Killer cells with MAGE-3 peptide against tumors expressing MAGE-3 protein.
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