首页> 外国专利> L-LEUCYL-L-LEUCINE METHYL ESTER TREATMENT OF DONOR LYPMHOCYTE INFUSIONS IN HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS

L-LEUCYL-L-LEUCINE METHYL ESTER TREATMENT OF DONOR LYPMHOCYTE INFUSIONS IN HEMATOPOIETIC STEM CELL TRANSPLANT PATIENTS

机译:L-亮氨酸-L-亮氨酸甲基酯处理造血干细胞移植患者体内供体淋巴细胞的注入

摘要

The present invention relates to a kind of for inhibiting the method for the graft versus host disease in allogeneic hematopoietic stem cell to transplant the cytotoxic T cell that (HSCT) patient eliminates selection in donor lymphocyte infusion (DLI) by using L- leucyls-L-Leu methyl ester (LLME). LLME is shown as inhibiting GVHD in through the animal models selectively induced programmed cell death in natural killer cells and cytotoxic T cell. When removing the concentration needed for the GVHD- inducing T cells before implantation, when useparated marrows are processed, application to the LLME of the clinical HSCT situations of people, however, being interfered by HSC toxicity. In the present invention, this problem is avoided by managing the LLME ex vivo treatments of the DLI of the transplanting below for the HSC that immunocyte exhausts. In this setting, the effect on clinical of the LLME on HSC between DLI is the result is that incoherent. In another embodiment, after the separation of CD34+ the stem cells then common management of the processed donor CD34- scores of LLME and untreated CD34+ stem cells, the risk of toxicity of population of stem cells is avoided by the LLME processing of external donor lymphocyte.
机译:本发明涉及一种抑制同种异体造血干细胞的移植物抗宿主病的方法,以移植通过使用L-亮氨酸-L消除HSCT患者消除供体淋巴细胞输注(DLI)选择的细胞毒性T细胞。 -Leu甲酯(LLME)。通过在自然杀伤细胞和细胞毒性T细胞中选择性诱导程序性细胞死亡的动物模型中,LLME显示出抑制GVHD的作用。当在植入前去除诱导GVHD的T细胞所需的浓度时,在处理过的骨髓时,将其应用于临床上具有临床HSCT状况的人的LLME,但是会受到HSC毒性的干扰。在本发明中,通过对免疫细胞衰竭的HSC进行以下移植的DLI的LLME离体处理的管理,可以避免该问题。在这种情况下,DLI之间的HSME对LLME临床的影响是其结果是不连贯的。在另一个实施方案中,在分离CD34 +干细胞然后共同处理经处理的供体CD34-LLME和未处理的CD34 +干细胞后,通过外部供体淋巴细胞的LLME处理避免了干细胞群毒性的风险。

著录项

  • 公开/公告号EP1274832A4

    专利类型

  • 公开/公告日2003-07-16

    原文格式PDF

  • 申请/专利权人 THOMAS JEFFERSON UNIVERSITY;

    申请/专利号EP20010918486

  • 发明设计人 KORNGOLD ROBERT;

    申请日2001-03-09

  • 分类号C12N5/06;C12N5/08;A61K38/05;

  • 国家 EP

  • 入库时间 2022-08-21 23:50:44

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