首页> 外国专利> MEDICAMENT TO INDUCE PROTECTION FROM GRAFT REJECTION BY A HOST'S IMMUNE SYSTEM BASED ON GENETICALLY ENGINEERED EUKARYOTIC CELLS COMPRISING DNA ENCODING TRANSMEMBRANE LAG-3 PROTEIN

MEDICAMENT TO INDUCE PROTECTION FROM GRAFT REJECTION BY A HOST'S IMMUNE SYSTEM BASED ON GENETICALLY ENGINEERED EUKARYOTIC CELLS COMPRISING DNA ENCODING TRANSMEMBRANE LAG-3 PROTEIN

机译:基于遗传工程化真核细胞的DNA编码跨膜LAG-3蛋白的宿主免疫系统,以防止移植物被排斥。

摘要

1. Use of genetically engineered eukaryotic cells comprising DNA encoding a transmembrane LAG-3 protein expressed on the surface of said cells resulting in the protection from graft rejection by a host's immune system. 2. Use as claimed in claim 1, wherein the DNA encoding a LAG-3 protein is exogenous. 3. Use as claimed in claim 1, wherein the DNA encoding a LAG-3 protein is endogenous and its expression is activated or modified through the targeted insertion of a regulator sequence and/or an amplifiable gene by homologous recombination. 4. Use as claimed in any of claims 1 to 3, wherein said cells are part of a tissue or organ to be transplanted. 5. Use as claimed in any of claims 1 to 3, wherein said cells are gene therapy host cells. 6. Use as claimed in claim 5, wherein gene therapy is somatic or "ex vivo" gene therapy. 7. Use as claimed in any of claims 1 to 6, wherein said cells are derived from transgenic animals. 8. Use as claimed in any of claims 1 to 7, wherein said cells are selected from myoblasts, fibroblasts, hematopoietic stem cells, embryonic stem cells, foetal liver cells, umbilical vein endothelial cells or CHO cells. 9. Use of a combination of genetically engineered eukaryotic cells comprising DNA encoding a transmembrane LAG-3 protein expressed on the surface of said cells and an additional immuno-suppressive agent, such as IL-10. TGFss or Fas ligand resulting in the protection from graft rejection by a host's immune system. 10. Use as claimed in claim 9, wherein said cells are derived from transgenic animals. 11. Use as claimed in claim 9 or 10, wherein said cells are selected from myoblasts, fibroblasts, hematopoietic stem cells, embryonic stem cells, foetal liver cells, umbilical vein endothelial cells or CHO cells. 12. Use of a combination of genetically engineered eukaryotic cells comprising DNA encoding a transmembrane LAG-3 protein expressed on the surface of said cells and the thymidine Kinase (tk) gene to be sensitive to the tk-gancyclovir suicide system resulting in the protection from graft rejection by a host's immune system. 13. Use as claimed in claim 12, wherein said cells are derived from transgenic animals. 14. Use as claimed in claim 12 or 13, wherein said cells are selected from myoblasts, fibroblasts, hematopoietic stem cells, embryonic stem cells, foetal liver cells, umbilical vein endothelial cells or CHO cells. 15. Use of a combination of genetically engineered eukaryotic cells comprising DNA encoding a transmembrane LAG-3 protein expressed on the surface of said cells in the manufacture of a medicament to induce protection from graft rejection by a host's immune system.
机译:1.遗传工程化的真核细胞的用途,所述真核细胞包含编码在所述细胞表面表达的跨膜LAG-3蛋白的DNA,从而保护其免受宿主免疫系统的移植排斥。 2.根据权利要求1的用途,其中编码LAG-3蛋白的DNA是外源的。 3.如权利要求1所述的用途,其中编码LAG-3蛋白的DNA是内源的,并且其表达通过同源重组通过靶向插入调节序列和/或可扩增基因而被激活或修饰。 4.根据权利要求1至3中任一项所述的用途,其中,所述细胞是待移植的组织或器官的一部分。 5.根据权利要求1-3中任一项的用途,其中所述细胞是基因治疗宿主细胞。 6.权利要求5的用途,其中基因治疗是体细胞或“离体”基因治疗。 7.权利要求1-6中任一项的用途,其中所述细胞衍生自转基因动物。 8.根据权利要求1至7中任一项所述的用途,其中所述细胞选自成肌细胞,成纤维细胞,造血干细胞,胚胎干细胞,胎儿肝细胞,脐静脉内皮细胞或CHO细胞。 9.基因工程的真核细胞的组合的用途,所述真核细胞包含编码在所述细胞表面表达的跨膜LAG-3蛋白的DNA和另外的免疫抑制剂,例如IL-10。 TGFss或Fas配体可防止宿主免疫系统排斥移植物。 10.根据权利要求9的用途,其中所述细胞衍生自转基因动物。 11.根据权利要求9或10所述的用途,其中所述细胞选自成肌细胞,成纤维细胞,造血干细胞,胚胎干细胞,胎儿肝细胞,脐静脉内皮细胞或CHO细胞。 12.遗传工程化的真核细胞的组合的用途,所述真核细胞包含编码在所述细胞表面表达的跨膜LAG-3蛋白的DNA和对tk-gancyclovir自杀系统敏感的胸苷激酶(tk)基因,从而保护其免受宿主免疫系统排斥移植物。 13.根据权利要求12的用途,其中所述细胞衍生自转基因动物。 14.如权利要求12或13所述的用途,其中,所述细胞选自成肌细胞,成纤维细胞,造血干细胞,胚胎干细胞,胎儿肝细胞,脐静脉内皮细胞或CHO细胞。 15.包含在所述细胞表面表达的编码跨膜LAG-3蛋白的DNA的基因工程真核细胞的组合在药物生产中的用途,所述药物诱导保护免受宿主免疫系统的移植排斥。

著录项

  • 公开/公告号EA003772B1

    专利类型

  • 公开/公告日2003-08-28

    原文格式PDF

  • 申请/专利权人 APPLIED RESEARCH SYSTEMS ARS HOLDING N.V.;

    申请/专利号EA19990000507

  • 发明设计人 BIFFONI MAURO;PAPOIAN RUBEN;

    申请日1996-11-29

  • 分类号C12N15/19;C07K14/52;A61K48/00;A61K38/19;C12N15/11;A61P37/06;

  • 国家 EA

  • 入库时间 2022-08-22 00:03:12

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