| Project/Area Number |
03454298
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | The University of Tokyo |
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Principal Investigator |
MIKAMO Shinsuke (1992-1993) The Institute of Medical Science, The University of Tokyo, Assistant, 医科学研究所, 助手 (10107435)
関口 守正 (1991) 東京大学, 医科学研究所, 教授 (60012712)
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| Co-Investigator(Kenkyū-buntansha) |
IKEBUCHI Kenji The Institute of Medical Science, The University of Tokyo, Lecturer, 医科学研究所, 講師 (20175194)
UCHIDA Hisanori The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (30050420)
SEKIGUCHI Morimasa The Institute of Medical Science, The University of Tokyo, Professor, 医科学研究所, 教授 (60012712)
美甘 晋介 東京大学, 医科学研究所, 助手 (10107435)
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| Project Period (FY) |
1991 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥3,400,000 (Direct Cost: ¥3,400,000)
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| Keywords | Cell transfer therapy / Immobilized CD3 / Immobilized IgG / Proliferation / Apoptosis / LAK / CD16 / CD25 / 癌治療 / リンパ球移入療法 / NK-LAK細胞 / 固相化CD3抗体 / 固相化ガンマグロブリン / CD16抗原 / CD25抗原 / AB型血清 / 肝転移 / 接着分子 / 癌細胞株 / 大腸癌 / 細胞株 / 初代培養 |
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| Research Abstract |
We have attempted to treat 11 patients with recurrent or metastatic cancer and 2 patients who recieved curative operation, by adoptive transfer of cultured autologous lymphocytes. Among 8 cancer bearing patients who received more than 8x10^9 cells, 6 of them responded at least transiently, including one PR case (case 6) and 2 cases with improved QOL (case 1,11).
Although cells were stimulated with immobilized CD3, highly activated NK cells were expanded in some cultures. NK cells were possively activated by IgG in the culture media, immobilized to the plastic wares during cultivation. In the case 6, large liver metastasis were regressed by combined transfer of highly activated NK cells and CTL,after ethanol injection and local chemotherapy had failed. Since the case was thought to be a good model, we intended to develop a new method for selective NK cell activation using immobilized LgG.NK cells exclusively adhered to the IgG coated ware, and some of them expanded while the others became shrinked or dead. Culture conditions, including co-existence of Mo and T cells, addition of IL2 and/or IL12, were tested. Then, a novel method to overcome activation induced cell death was developed. NK cells from a healthy donor were activated by the method and a NK culture of high purity was obtained expanding 1000 fold. The datails of the method will be reported elsewhere.
NK cells reportedly reach to foci of viral infection at first and may trigger CTL reaction. It might be the case in tumor immunity, provided the patient is not anergy to the tumor antigen. Combined transfer of NK and CTL might bring forward a new strategy for treatment of advanced cancer.
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