Title:
THIOPURINE-HYPERSENSITIVE CHIMERIC-ANTIGEN-RECEPTOR GENE-MODIFIED LYMPHOCYTE
Document Type and Number:
WIPO Patent Application WO/2018/079497
Kind Code:
A1
Abstract:
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.
Inventors:
NAKAZAWA YOZO (JP)
MATSUDA KAZUYUKI (JP)
MORITA DAISUKE (JP)
MURAMATSU HIDEKI (JP)
OKUNO YUSUKE (JP)
TAKAHASHI YOSHIYUKI (JP)
MATSUDA KAZUYUKI (JP)
MORITA DAISUKE (JP)
MURAMATSU HIDEKI (JP)
OKUNO YUSUKE (JP)
TAKAHASHI YOSHIYUKI (JP)
Application Number:
PCT/JP2017/038217
Publication Date:
May 03, 2018
Filing Date:
October 23, 2017
Export Citation:
Assignee:
UNIV SHINSHU (JP)
UNIV NAGOYA NAT UNIV CORP (JP)
UNIV NAGOYA NAT UNIV CORP (JP)
International Classes:
C12N15/09; A61K31/52; A61K35/17; A61P35/00; C12N5/10; C12N15/113
Other References:
JONES BENJAMIN S. ET AL.: "Improving the safety of cell therapy products by suicide gene transfer", FRONTIERS IN PHARMACOLOGY, vol. 5, 2014, XP055340558
MARIN VIRNA ET AL.: "Comparison of Different Suicide- Gene Strategies for the Safety Improvement of Genetically Manipulated T cells", HUMAN GENE THERAPY METHODS, vol. 23, 2012, pages 376 - 386, XP009171601, DOI: doi:10.1089/hgtb.2012.050
FUKAO, DAISUKE ET AL.,: "A case of T-cell acute lymphoblastic leukemia in an NUDT15-variant patient who developed severe myelosuppression caused by 6-mercaptopurine during maintenance therapy", THE JAPANESE JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY, vol. 53, no. 2, July 2016 (2016-07-01), pages 139 - 142, XP055606753
MARIN VIRNA ET AL.: "Comparison of Different Suicide- Gene Strategies for the Safety Improvement of Genetically Manipulated T cells", HUMAN GENE THERAPY METHODS, vol. 23, 2012, pages 376 - 386, XP009171601, DOI: doi:10.1089/hgtb.2012.050
FUKAO, DAISUKE ET AL.,: "A case of T-cell acute lymphoblastic leukemia in an NUDT15-variant patient who developed severe myelosuppression caused by 6-mercaptopurine during maintenance therapy", THE JAPANESE JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY, vol. 53, no. 2, July 2016 (2016-07-01), pages 139 - 142, XP055606753
Attorney, Agent or Firm:
HAGINO Mikiharu (JP)
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