2001 Fiscal Year Final Research Report Summary
Establishment of antigen-specific immunotherapy with artificial lymphocytes genetically engineered by antigen specific receptor and functional genes.
| Project/Area Number |
11357006
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
内科学一般
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YAMAMOTO Kazuhiko The University of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (80191394)
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| Co-Investigator(Kenkyū-buntansha) |
SAWADA Tetsuji The University of Tokyo, Facuulty of Medicin, Assistant, 医学部・附属病院, 助手 (50235470)
DOHI Makoto The University of Tokyo, Facuulty of Medicin, Assistant, 医学部・附属病院, 助手 (60222155)
MISAKI Yoshiikata The University of Tokyo, Facuulty of Medicin, Lecturer, 医学部・附属病院, 講師 (60219615)
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| Project Period (FY) |
1999 – 2001
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| Keywords | Immune diseases / antigen-specific immunotherapy / T cell receptor / gene transduction / cell therapy |
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| Research Abstract |
Antigen-specific T lymphocytes should be clonally accumulated in order to perform their roles. We have established a system to detect such accumulated T lymphocytes in a lymphocyte population using RT-PCR and SSCP method on T cell receptor (TCR). We then extended our work to reconstitute the TCR function in vitro. With this method, artificial lymphocytes for antigen-specific immunotherapy could be generated. Two technical difficulties exist. They are the pairing of two TCR messages from a single T lymphocyte and induction of multiple genes into lymphocytes from a recipient for the therapy. We have tried to develop several of these methods and found that a single cell sorting method is so far working for the pairing. Regarding the gene transfer to lymphocytes, a retrovirus vector would be the best. We have succeeded in obtaining more than 50 % of transduction of a single gene. Therefore, more than 10 % of the treated lymphocyte population could express 3 genes altogether. We are now performing experimental immunotherapy for lupus nephritis of NZB/W F1 mice using these established methods.
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[Publications] Yamada R., Tanaka T., Unoki K., Nagai T., Sawada T., Ohnishi Y., Isunoda T., Yukioka M., Maeda A., Suzuki K., Tateishi H., Ochi T., Nakamura Y. and Yamamoto K.: "Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihood estimation of combinatorial effect that two genetic loci have on susceptibility to the disease"Am.J.Hum.Genet.. 68. 674-685 (2001)
Description
「研究成果報告書概要(欧文)」より
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