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METHOD FOR PRODUCING FOREIGN ANTIGEN RECEPTOR GENE-INTRODUCED CELL NEW

外国特許コード F200010054
整理番号 6118
掲載日 2020年5月15日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2019JP029537
国際公開番号 WO 2020022512
国際出願日 令和元年7月26日(2019.7.26)
国際公開日 令和2年1月30日(2020.1.30)
優先権データ
  • 特願2018-140523 (2018.7.26) JP
発明の名称 (英語) METHOD FOR PRODUCING FOREIGN ANTIGEN RECEPTOR GENE-INTRODUCED CELL NEW
発明の概要(英語) Provided are: a method for producing an antigen receptor gene-introduced cell, the method comprising a step for introducing a foreign T cell receptor (TCR) or chimeric antigen receptor (CAR) gene such that expression is accomplished under the control of a TCR expression controlling mechanism of a material cell; and a material cell for introducing a foreign antigen receptor gene having, on a TCR gene locus in the order of, from the upstream side, a promoter sequence in a V-region of the TCR gene locus, a drug-resistant gene or a reporter gene or a known TCR or CAR gene, and an enhancer sequence in a C-region of the TCR gene locus.
従来技術、競合技術の概要(英語) BACKGROUND ART
Disease-specific T cell receptor (TCR) or chimeric antigen receptor (CAR) of the mature T antigen receptor gene introduced into a cell which can be used for the treatment of a disease have been proposed. CAR-T cells introduced particular CAR treatment method has already been approved, has been in clinical use. T cells from a patient as a gene and a cell is used, a so-called self-implantation system. The introduction of the gene in the genome using lentivivus retrovirus or randomly introduced. Gene may be introduced by such methods, may damage the normal gene, such as a cancer gene and the risk of activation. Genome editing techniques while mature T reconstructed TCR loci of the cells in that the knocked CAR method reported in this paper (Nature, 543:113, 2017). In this way the physiological expression of the transgene is controlled so that the TCR, and thus more CAR-T cells produced is said to be high.
Different from the above approach, the inventors have found that the level of the pluripotent stem cells has been proposed a method of introducing the TCR (Patent Document 1). This is T from pluripotent stem cells and cells that is the strategy to be used by a cell-based therapies. CAR gene level of pluripotent stem cells in the TCR is also a method of introducing, by m. Sadelain has been proposed (Patent Document 2 and Non-Patent Document 1).
Until now, if the TCR CAR gene is a gene, gene loci T TCR of the cells other than a report that is not a knock. T cells other than the gene locus TCR reconstruction does not occur. TCR reconstruction of gene loci is not CAR TCR gene is knocked or is not to be reported.
, Recombinase-mediated Cassette Exchange(RMCE) method as the method of introducing the gene is known. This is on a gene of the cell such as a cassette deck in the particular portion of the sequence of foreign recombinant (cassette tape) into the structure in the target cell in advance, such as Cre Flippase and the recombinant enzyme introduced so as to exchange a cassette tape using a technique. T cell lines may be applied to a (non-patent document 2) in the document. However, this mechanism is introduced into the T cell gene loci that is not an example.
CAR TCR gene or genes, gene-introduced into the cells of the mature T general strategy. On the other hand, the inventors of the present invention a part of the TCR at the level of introducing a pluripotent stem cell has been proposed a method (JP-3-5). The method for introducing the gene for the CAR has been proposed. In such methods, when a gene is CAR and TCR, such as a random genome pmBCmCNluci introduced into the method that is employed. However, the original TCR and TCR gene knock CAR gene loci is the physiological expression pattern can be expected. In fact, already mature T cell re-configuration of the locus of the gene has been reported that CAR. TCR cells generally has a locus. However, T cells other than the gene locus TCR reconstruction does not occur. Thus T cells other than the material of the case of using the cell therapy, gene loci TCR simply by only introducing foreign TCR/CAR do not. Further, many types of TCR/CAR gene and is used for the expected, correct each knock on a required region of the time and cost it becomes a problem.
  • 出願人(英語)
  • ※2012年7月以前掲載分については米国以外のすべての指定国
  • KYOTO UNIVERSITY
  • SHIGA UNIVERSITY OF MEDICAL SCIENCE
  • 発明者(英語)
  • KAWAMOTO, Hiroshi
  • AGATA, Yasutoshi
  • NAGANO, Seiji
  • TERADA, Koji
  • MASUDA, Kyoko
国際特許分類(IPC)
指定国 National States: AE AG AL AM AO AT AU AZ BA BB BG BH BN BR BW BY BZ CA CH CL CN CO CR CU CZ DE DJ DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JO JP KE KG KH KN KP KR KW KZ LA LC LK LR LS LU LY MA MD ME MG MK MN MW MX MY MZ NA NG NI NO NZ OM PA PE PG PH PL PT QA RO RS RU RW SA SC SD SE SG SK SL SM ST SV SY TH TJ TM TN TR TT TZ UA UG US UZ VC VN ZA ZM ZW
ARIPO: BW GH GM KE LR LS MW MZ NA RW SD SL SZ TZ UG ZM ZW
EAPO: AM AZ BY KG KZ RU TJ TM
EPO: AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR
OAPI: BF BJ CF CG CI CM GA GN GQ GW KM ML MR NE SN ST TD TG
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