1998 Fiscal Year Final Research Report Summary
Development of a tumor vaccine using a membrane attached form of interleukin-15
| Project/Area Number |
09670782
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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 |
Pediatrics
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| Research Institution | Tohoku University |
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Principal Investigator |
MINEGISHI Masayoshi Institute of Development, Aging and Cancer, Department of Pediatric Oncology Tohoku University Associate Professor, 加齢医学研究所・発達病態研究分野, 助教授 (20211592)
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| Co-Investigator(Kenkyū-buntansha) |
KONNO Tasuke Institute of Development, Aging and Cancer, Department of Pediatric Oncology Toh, 加齢医学研究所・発達病態研究分野, 前教授 (00004846)
KUMAKI Satoru Institute of Development, Aging and Cancer, Department of Pediatric Oncology Toh, 加齢医学研究所・発達病態研究分野, 助手
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| Project Period (FY) |
1997 – 1998
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| Keywords | interleukin-15 / acute GVHD / gammac chain / NK cell / retrovirus vector |
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| Research Abstract |
To evaluate factors affect IL-15 production, we examined serum levels of IL-15 in children who had received allogeneic BMT as a model of immune reconstitution. We observed prolonged secretion of IL-15 only in patients with grade III or IV acute OVHD.Since 11-15 is able to activate antigen-stimulated T cells and NK cells, IL-15may play an important role in the development of severe forms of acute GVHD.We also examined functional role of 11-15 using a mutant gammac chain (A156V) isolated from an atypical X-SCID patient who lacked T cells but has normal NK activity. We demonstrate that the mutant gammac chain transduces an IL-15-induced signal. Therefore, the mutant gammac chain might be partially functional for NK-cell development and as a result the patient has NK cells. IL-15 protein has been harder to detect, although IL-15 mRNA is found almost everywhere. One of the reasons for this inefficient translation is the unusually long IL-15 leader. Thus, we replaced the leader sequence with that of IL-2and inserted into a retrovirus vector, pLXIN.With this construct, IL-15 was produced much more efficiently than with the wild type IL-15 cDNA.In addition, a cell surface-bound form of IL-15 was constructed with this highly efficient IL-15 plus transmembrane region of the chain. The chimeric protein failed to express on the cell surface. We speculated that the IL-2 leader might interrupt the cell surface expression and now replacing the leader sequence with that of the gammac chain. Meanwhile, we are establishing an autocrine cell line by infection of the retrovirus encoding the highly efficient IL-15 cDNA to cells obtained from a patient with stem cell leukemia, which express a high level of functional IL-15 receptor. We are planning to develop a tumor vaccine using the retrovirus vectors and the autorine cell line described above.
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[Publications] Hossain A., Tsuchiya S., Minegishi M., Osada M., Ikawa S., Tezuka FA., Kaji M., Konno T., Watanabe M.and Kikuchi H.: "The Ah receptor is not involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated apoptosis in human leukemic T cell lines." J Biol Chem. 273. 19853-19858 (1998)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Kawamura M., Ohnishi H., Guo SX., Sheng XM., Minegishi M., Hanada R., Horibe K., Hongo T., Kaneko Y., Bessho F., Yanagisawa M., Sekiya T., Hayashi Y.: "Alterations of the p53, p21, p16, p15 and RAS genes in childhood T-cell acute lymphoblastic leukemia." Leukemia Res.23. 115-126 (1999)
Description
「研究成果報告書概要(欧文)」より
