2004 Fiscal Year Final Research Report Summary
Novel immunogene therapy for hematopoietic malignancies
| Project/Area Number |
15390301
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Hematology
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| Research Institution | Ehime University |
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Principal Investigator |
YASUKAWA Masaki Ehime University, School of Medicine, Associate Professor, 医学部, 助教授 (60127917)
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| Co-Investigator(Kenkyū-buntansha) |
YAKUSHIJIN Yoshihiro Ehime University, School of Medicine, Instructor, 医学部, 助手 (30294797)
UCHIDA Hiroyuki Ehime University, University Hospital, Instructor, 医学部附属病院, 助手 (80359926)
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| Project Period (FY) |
2003 – 2004
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| Keywords | hematopoietic malignancies / cytotoxic T lymphocyte / WT1 / cancer vaccine / immunodefcient mice / T-cell receptor |
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| Research Abstract |
We performed studies on immunogene therapy for hematopoietic malignanicies. The data obtained from the series of study are as follows. 1) Myeloma cells are sensitive to perforin-dependent cytotoxicity mediated by WT1-specifici cytotoxic T lymphocytes (CTLs). 2)There is a difference in the control of perforin expression between CD4^+ and CD8^+ CTLs ; that is, perforin is expressed constitutively in memory CD8^+ CTLs, but is dependent on cell activation in memory CD4^+ CTLs. 3)T-cell receptor (TCR) α and β genes obtained from an HLA-A24-restricted, WT1 peptide-specific CTL clone were lentivirally transduced to polyclonally-activated T lymphocytes. TCR gene-transduced CD4+ and CD8+ T lymphocytes showed HLA-A24-restricted and WT1-specific reactivity against leukemia cells. 4)The WT1-derived epitope recognized by HLA-DP5-restricted CD4+ T-cell clone was identified. WT1-specific CD4+ T-cell clone exerted the perforin-dependent cytotoxicity against leukemia cells. 5)Phase I clinical study of cancer peptide vaccine using WT1-derived and hTERT-derived peptides has been continued. 6) Human immune system was constructed in the novel immundeficient mice by transplantation of human hematopoietic stem cells.
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Research Products
(12 results)
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[Journal Article] Human cord blood- and bone marrow-derived CD34^+ cells regenerate gastrointestinal epithelial cells.2004
Author(s)
Ishikawa, F., Yasukawa, M., Yoshida, S., Shimoda, K., Shimoda, S., Nakamura, K., Nagatoshi, Y., Kanemaru, T., Kawano, N., Nagafuji, K., Miyamoto, T., Fukuda, T., Okamura, J., Shultz, L.D., Harada, M.
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Journal Title
FASEB J. 18
Pages: 1958-1960
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Identification of novel MUNC13-4 mutations in familial hemophagocytic lymphohistiocytosis and functional analysis of MUNC 13-4-deficient cytotoxic T lymphocytes.2004
Author(s)
Yamamoto, K., Ishii, E., Sako, M., Ohga, S., Furuno, K., Suzuki, N., Ueda, I., Imayoshi, M., Yamamoto, S., Morimoto, A., Takada, H., Hara, T., Imashuku, S., Sasazuki, T., Yasukawa, M.
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Journal Title
J.Med.Genet. 41
Pages: 763-767
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Myeloma cells are highly sensitive to granule exocytosis pathway mediated by WT1-specific cytotoxic T lymphocytes.2004
Author(s)
Azuma, T., Otsuki, T., Kuzushima, K., Froelich, C., Fujita, S., Yasukawa, M.
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Journal Title
Clin.Cancer Res. 10
Pages: 7402-7412
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Essential roles of perforin in antigen-specific cytotoxicity mediated by human CD4^+ T lymphocytes : analysis using the combination of hereditary perforin-deficient effector cells and Fas-deficient target cells.2003
Author(s)
Yanai, F., Ishii, E., Kojima, K., Hasegawa, A., Azuma, T., Hirose, S., Suga, N., Mitsudome, A., Zaitsu, M., Ishida, Y., Shirakata, Y., Sayama, K., Hashimoto, K., Yasukawa, M.
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Journal Title
J.Immunol. 170
Pages: 2205-2213
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Generation of human tumor-specific, HLA class I-restricted Th1 and Tc1 cells by cell engineering with tumor peptide-specific T cell receptor genes.
Author(s)
Tsuji, T., Yasukawa, M., Matsuzaki, J., Ohkuri, T., Chamoto, K., Azuma, T., Niiya, H., Miyoshi, H., Takeshima, T., Ikeda, H., Nishimura, T.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Genetic subtypes of familial hemophagocytic lymphohistiocytosis : correlations with clinical features and cytotoxic T lymphocyte/natural killer cell functions.
Author(s)
Ishii, E., Ueda, I., Shirakawa, R., Yamamoto, K., Horiuchi, H., Ohga, S., Furuno, K., Morimoto, A., Imayoshi, M., Ogata, Y., Sako, M., Koike, K., Sakata, A., Takada, H., Hara, T., Imashuku, S., Sasazuki T., Yasukawa, M.
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Journal Title
Description
「研究成果報告書概要(欧文)」より
