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THIOPURINE-HYPERSENSITIVE CHIMERIC-ANTIGEN-RECEPTOR GENE-MODIFIED LYMPHOCYTE NEW

外国特許コード F180009459
整理番号 (S2017-0066-N0)
掲載日 2018年7月31日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2017JP038217
国際公開番号 WO 2018079497
国際出願日 平成29年10月23日(2017.10.23)
国際公開日 平成30年5月3日(2018.5.3)
優先権データ
  • 特願2016-209066 (2016.10.25) JP
発明の名称 (英語) THIOPURINE-HYPERSENSITIVE CHIMERIC-ANTIGEN-RECEPTOR GENE-MODIFIED LYMPHOCYTE NEW
発明の概要(英語) The present invention addresses the problem of providing a novel suicide gene system which allows for control of a chimeric-antigen-receptor gene-modified lymphocyte after being administered using a highly safe method, in order to further advance clinical applications of CAR therapies. According to the present invention, a genetically modified lymphocyte which expresses a chimeric antigen receptor is prepared by introducing, into a target cell, a target antigen-specific chimeric antigen receptor gene, and a first nucleic acid construct which intracellularly produces an siRNA which targets the NUDT15 gene and/or a second nucleic acid construct which intracellularly produces an siRNA which targets the TPMT gene.
特許請求の範囲(英語) [claim1]
1. Along with the gene specific to the target antigen chimeric antigen receptor, NUDT15 siRNA targeting a target gene is produced in the cell to the first and/or nucleic acid construct of claim 1 TPMT siRNA targeting a target gene in a cell to a target cell for generating a first step of introducing the nucleic acid construct of claim 2, including, chimeric antigen receptor gene expressing a method for preparing a modified lymphocytes.
[claim2]
2. For the target antigen specific chimeric antigen receptor gene, the second nucleic acid construct of claim 1, 2 and the introduction of a nucleic acid construct, are performed by a transposon, according to claim 1 preparation method.
[claim3]
3. A transposon transposon piggyBac method in the method, according to claim 2 preparation method.
[claim4]
4. For the target antigen specific chimeric antigen receptor gene, 1 of the first and/or the second nucleic acid construct is a nucleic acid construct 2 mounted on the same vector, the vector is incorporated into a target cell that, according to any one of claims 1-3 method for the preparation of.
[claim5]
5. T is the target cell is a cell, according to any one of claims 1-4 preparation according to the method.
[claim6]
6. And expressing a chimeric antigen receptor, and/or siRNA targeting a target gene NUDT15 TPMT gene targeting siRNA targeting siRNA is generated within the cell, to any one of claims 1-5 obtained by the method of preparing the genetically modified lymphocytes.
[claim7]
7. A genetic modification according to claim 6 comprising a therapeutically effective amount of lymphocytes, cell preparation.
[claim8]
8. According to claim 6 lymphocytes genetic modification, a therapeutically effective amount, comprising the step of administering to the patient's cancer, cancer therapy.
[claim9]
9. Wherein the patient receives treatment method according to claim 8 FZDlO thiopurine CAMPTO formulation, wherein the genetically modified lymphocytes of inducing cell death.
[claim10]
10. For the target antigen specific chimeric antigen receptor gene chimer antigen receptor expression with the cassette, NUDT15 siRNA targeting a target gene is produced in the cell to the first and/or nucleic acid construct of claim 1 TPMT siRNA targeting a target gene in a cell comprising the nucleic acid construct of claim 2 for generating a first siRNA expression cassette is mounted on the vector.
[claim11]
11. A chimeric antigen receptor expression cassette is the cassette and a pair of transposon inverted repeat siRNA sequence comprises structure sandwiched between, according to claim 10 vector.
[claim12]
12. A vector according to claim 11, an expression vector transposase, chimeric antigen receptor gene expressing the lymphocytes Amethodaccording kit.
[claim13]
13. For the target antigen specific chimeric antigen receptor gene expression cassette antigen receptor chimer vector mounted, NUDT15 siRNA targeting a target gene is produced in the cell to the first and/or nucleic acid construct of claim 1 TPMT siRNA targeting a target gene in a cell comprising the nucleic acid construct of claim 2 for generating a first siRNA vector expression cassette mounted thereon, comprising, chimeric antigen receptor gene expressing the lymphocytes Amethodaccording kit.
[claim14]
14. A chimeric antigen receptor expression cassette is sandwiched between a pair of transposon inverted repeat sequence comprises a structure, a pair of transposon siRNA expression cassette in a direction opposite to a sequence repeated a sandwiched structure, further comprising transposase expression vector, according to claim 13 preparation kit.
[claim15]
15. For the target antigen specific chimeric antigen receptor gene expression cassette chimeric antigen receptor mounted on the second vector 1, NUDT15 siRNA targeting a target gene in a cell comprising a nucleic acid construct of claim 1 for generating a first expression cassette 1siRNA vector and mounted, TPMT siRNA targeting a target gene in a cell comprising a nucleic acid construct of claim 2 for generating a first 2siRNA mounted and vector expression cassette, comprising, chimeric antigen receptor gene expressing the lymphocytes Amethodaccording kit.
[claim16]
16. A chimeric antigen receptor expression cassette is sandwiched between a pair of transposon inverted repeat sequence provided with the structure, in a direction opposite to the first pair of transposon 1siRNA expression cassette is derived from a sequence repeated a sandwiched structure, in a direction opposite to the first pair of transposon 2siRNA expression cassette is derived from a sequence repeated a sandwiched structure, further comprising transposase expression vector, according to claim 15 preparation kit.
[claim17]
17. Transposase transposase piggyBac, claim 12, 14, any one of claims 16 wherein the preparation kit.
  • 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
  • SHINSHU UNIVERSITY
  • NAGOYA UNIVERSITY
  • 発明者(英語)
  • NAKAZAWA YOZO
  • MATSUDA KAZUYUKI
  • MORITA DAISUKE
  • MURAMATSU HIDEKI
  • OKUNO YUSUKE
  • TAKAHASHI YOSHIYUKI
国際特許分類(IPC)
指定国 (WO201879497)
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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