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CAR EXPRESSION VECTOR AND CAR-EXPRESSING T CELLS

外国特許コード F160008803
整理番号 (S2014-1580-N0)
掲載日 2016年8月4日
出願国 世界知的所有権機関(WIPO)
国際出願番号 2015JP005080
国際公開番号 WO 2016056228
国際出願日 平成27年10月6日(2015.10.6)
国際公開日 平成28年4月14日(2016.4.14)
優先権データ
  • 特願2014-208200 (2014.10.9) JP
発明の名称 (英語) CAR EXPRESSION VECTOR AND CAR-EXPRESSING T CELLS
発明の概要(英語) The present invention addresses the problem of providing chimeric antigen receptor (CAR)-expressing T cells that express a CAR and also express a T cell immunological function promoting factor, and that have a strong immunity-inducing effect and high antitumor activity. The present invention also addresses the problem of providing a CAR expression vector for producing such CAR-expressing T cells. This CAR expression vector contains a nucleic acid that codes for a CAR, and a nucleic acid that codes for a T cell immunological function promoting factor, wherein the nucleic acid that codes for the T cell immunological function promoting factor comprises either: the nucleic acid that codes for interleukin-7 and the nucleic acid that codes for CCL19; a nucleic acid that codes for a dominant-negative mutant of SHP-1; or a nucleic acid that codes for a dominant-negative mutant of SHP-2. CAR-expressing T cells into which said CAR expression vector has been introduced are produced.
従来技術、競合技術の概要(英語) BACKGROUND ART
Chimeric antigen receptors (Chimeric Antigen Receptor: hereinafter, also referred to as' CAR ') is, the cell surface of cancer cells and single-chain antibody that recognizes an antigen, T cells induces the activation of the signaling region fuzed to the artificial chimeric protein. As shown in Fig. 1, does not have a tumour-reactive T cells normal peripheral blood (peripheral blood T lymphocytes) to by introducing a gene encoding CAR, CAR T cells capable of expressing CAR expression (hereinafter, simply referred to as' CAR-T cells' also referred to as) and producing a large number of possible. Such CAR-T cell is a tumor has reactivity, major histocompatibility complex (MHC) without depending on the interaction of cancer cells and guided to the injury.
Administration of the cells by cancer immunotherapy CAR-T, more specifically, T cells were harvested from the patient, such T cells by introducing a gene encoding CAR is amplified, again introduced into the patient therapy (see non-patent document 1) is, worldwide clinical trials has progressed, such as a malignant tumor such as lymphoma or leukemia hematopoietic shows efficacy in a result is obtained.
In recent years, various CAR-T cell studies have been performed. For example, an antigen-binding region and the transmembrane region CD19 cell co-stimulatory signal region 4-1BB, consisting of a nucleic acid encoding CAR CD3 ζ signal region comprising a modified human T cells a pharmaceutical composition comprising autologous (see Patent Document 1) or, 1 binds to the cell one or more cancer of the tagged protein of the formulation is administered to a subject simultaneously or separately, the tagged proteins bound to the, cancer cell death-inducing 1 one or more therapeutic effective anti tagukimera T (AT-CAR) antigen receptor (see Patent Document 2) expression and cell population, the antigen-binding domain of the human antibody 139, an extracellular hinge domain, a transmembrane domain cells, a cellular signaling domain and an intracellular T, encoding a chimeric antigen receptor (see Patent Document 3) cells containing the nucleic acid or, a nucleic acid sequence encoding a chimeric antigen-receptors or a cell that contains a, the chimeric antigen receptor antigen-binding domain, a transmembrane domain cells, co-stimulatory signal transfer region, and, comprises the amino acid sequence SEQ ID NO:24 CD3 ζ signaling domain (see Patent Document 4) or a cell containing, on the cell surface CD19 expression and possesses specific chimeric receptor, the chimeric receptor of the effector function of immune cells for intracellular signaling domain, a transmembrane domain and at least one cell 1 1 and at least one extracellular domain, the extracellular domain containing receptor CD19, genetically engineered cells produced CD19 (see Patent Document 5) specific T and, the intracellular domain as glucocorticoid induced tumor necrosis factor receptor (GITR) an intracellular domain of the chimeric antigen receptor has been introduced a nucleic acid encoding a chimeric antigen receptor expressing cell line (see Patent Document 6) is proposed.
However, the survival of cells in vivo CAR-T efficiency is low, or induced by an endogenous CAR-T T cell activation and tumor cells is insufficient and a problem in that local accumulation at the, a tumor having cancer cells immune evasion mechanism PD-1 PD-L1/signal via the second immunosuppressive microenvironment and cancer TGF-β in or secreted immunosuppressive factors such as IL-10 CAR-T cell activity by inhibiting the problem with past technology has not been solved. Therefore, sufficient treatment effect is not species and cancer cases exist, for more effective CAR-T cells, and cells for making such CAR-T has been desired in the preparation of the expression vector.
  • 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
  • YAMAGUCHI UNIVERSITY
  • 発明者(英語)
  • TAMADA, Koji
  • SAKODA, Yukimi
  • ADACHI, Keishi
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 DK DM DO DZ EC EE EG ES FI GB GD GE GH GM GT HN HR HU ID IL IN IR IS JP KE KG KN KP KR 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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