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    Genetically modified CD34-negative adherently growing stem cells and their use in gene therapy
    2.
    发明授权
    Genetically modified CD34-negative adherently growing stem cells and their use in gene therapy 有权
    遗传修饰的CD34阴性粘附生长的干细胞及其在基因治疗中的应用

    公开(公告)号：US06361997B1

    公开(公告)日：2002-03-26

    申请号：US09743904

    申请日：2001-02-24

    申请人： Ralf Huss

    发明人： Ralf Huss

    IPC分类号： C12N510

    CPC分类号： C12N5/0647 ,  A61K48/00 ,  A61K2035/124 ,  C12N2501/23 ,  C12N2510/00

    摘要： The invention relates to the use of genetically modified, very early haematopoietic and mesenchymal stem cells (negative for the expression of the surface molecule CD34) in the individual gene therapy of mono- or oligogenetic diseases or in cell therapy. Autologous CD34-negative adherently growing stem cell cultures from the peripheral blood of the patient are applied and efficiently tranfected or infected with genetic constructs. The gene products of these genes should substitute defective or absent proteins or factors in the patient organism in the long term. After expansion, the autologous stem cells can also be used for cell therapy (organ replacement therapy).

    摘要翻译： 本发明涉及遗传修饰的非常早期的造血和间充质干细胞（对表达分子CD34的表达阴性）在单基因或寡发生疾病或细胞治疗的单独基因治疗中的用途。 应用来自患者外周血的自体CD34阴性附着生长的干细胞培养物，并有效地转染或用遗传构建体感染。 这些基因的基因产物应该长期替代患者生物体中有缺陷或不存在的蛋白质或因子。 扩张后，自体干细胞也可用于细胞治疗（器官置换治疗）。

    Chemokine-Mucin Fusions Linked to Glycosylphosphatidylinositol (GPI)-Anchors in Tissue Regeneration and as Tumour Immune Adjuvants
    4.
    发明申请
    Chemokine-Mucin Fusions Linked to Glycosylphosphatidylinositol (GPI)-Anchors in Tissue Regeneration and as Tumour Immune Adjuvants 审中-公开
    与糖基磷脂酰肌醇（GPI）相关的趋化因子 - 粘蛋白融合蛋白在组织再生和肿瘤免疫佐剂中的作用

    公开(公告)号：US20120208769A1

    公开(公告)日：2012-08-16

    申请号：US12085882

    申请日：2006-11-30

    申请人： Peter Jon Nelson ,  Ralf Huss ,  Hermann-Josef Grone

    发明人： Peter Jon Nelson ,  Ralf Huss ,  Hermann-Josef Grone

    IPC分类号： A61K38/19 ,  C12N5/10 ,  C12N1/21 ,  C12N15/62 ,  A61P35/00 ,  A61K31/711 ,  C07K19/00 ,  C12N5/02 ,  C12N15/63

    CPC分类号： C07K14/524 ,  A61K38/00 ,  C07K14/4727 ,  C07K2319/00

    摘要： The present invention relates to chemokine-mucin fusions linked to glycosylphosphatidylinositol (GPI)-anchors and their use as anti-cancer adjuvants and as agents in tissue regeneration and suppression of vascular damage. GPI-linked chemokines are incorporated in the surface membrane of tumour cells and effect a recruitment of cytotoxic immune cells to the tumour site following injection in vivo. Leukocytes, cytotoxic T-cells and NK cells target the chemokine-GPI-anchored tumour cells and modulate cell-mediated lysis of the tumour cells. The efficiency of GPI-anchoring and modulation of immune cells can be further enhanced by linking the chemokine to a mucin domain followed by the GPI-anchor. The GPI-anchored chemokines, with or without mucin domain, are remarkably useful for the inhibition of tumour growth, tissue regeneration, and suppression of acute vascular damage to allografts.

    摘要翻译： 本发明涉及与糖基磷脂酰肌醇（GPI） - 锚定相关的趋化因子 - 粘蛋白融合物，以及它们作为抗癌辅助剂的用途，以及作为组织再生和抑制血管损伤的药剂。 将GPI连接的趋化因子并入肿瘤细胞的表面膜中，并且在体内注射后可以诱导细胞毒性免疫细胞到肿瘤部位。 白细胞，细胞毒性T细胞和NK细胞靶向趋化因子-GPI锚定的肿瘤细胞并调节细胞介导的肿瘤细胞裂解。 GPI锚定和调节免疫细胞的效率可以通过将趋化因子连接到粘蛋白结构域，然后连接GPI锚点来进一步增强。 具有或不具有粘蛋白结构域的GPI锚定趋化因子对于抑制肿瘤生长，组织再生和抑制同种异体移植物的急性血管损伤是非常有用的。

    Tissue inhibitor of metalloproteinases (TIMP) linked to glycosylphosphatidylinositol (GPI)-anchors for treatment of cancer and skin lesions
    8.
    发明授权
    Tissue inhibitor of metalloproteinases (TIMP) linked to glycosylphosphatidylinositol (GPI)-anchors for treatment of cancer and skin lesions 有权
    与糖基磷脂酰肌醇（GPI）连接的金属蛋白酶组织抑制剂（TIMP）用于治疗癌症和皮肤病变

    公开(公告)号：US09255139B2

    公开(公告)日：2016-02-09

    申请号：US11992213

    申请日：2006-09-20

    申请人： Ralf Huss ,  Peter J. Nelson

    发明人： Ralf Huss ,  Peter J. Nelson

    IPC分类号： A61K38/57 ,  C07K14/81 ,  C07H21/04 ,  C12N15/63 ,  C12N5/10 ,  A61P35/00 ,  A61K47/48

    CPC分类号： A61K38/57 ,  A61K38/1709 ,  A61K47/544 ,  A61K47/549 ,  A61K47/62 ,  C07K14/8146

    摘要： The present invention relates to fusion constructs of glycosylphosphatidylinositol (GPI)-anchored tissue inhibitors of metalloproteinases (TIMPs) and their use for the treatment of cancer and in regenerative medicine. By this approach, the GPI-anchored TIMP proteins are incorporated into the surface membrane of tumor cells and render tumor cells sensitive to FAS-induced apoptosis. Furthermore, the fusion constructs of the present invention are effective agents useful in wound healing applications. In one embodiment, the TIMP is linked to mucin followed by GPI in order to enhance surface presentation. The use of GPI to link TIMP renders the resulting fusion protein particularly useful as an anti-cancer agent for the treatment of cancer, and, in particular, any residual cancer following an incomplete surgical resection of primary tumors in an individual.

    摘要翻译： 本发明涉及糖基磷脂酰肌醇（GPI） - 金属蛋白酶组织抑制剂（TIMP）的融合构建体及其在再生医学中的应用。 通过这种方法，GPI锚定的TIMP蛋白被并入肿瘤细胞的表面膜，并使肿瘤细胞对FAS诱导的细胞凋亡敏感。 此外，本发明的融合构建体是可用于伤口愈合应用的有效试剂。 在一个实施方案中，TIMP与粘蛋白连接，然后与GPI连接，以增强表面表达。 使用GPI连接TIMP使所得到的融合蛋白特别可用作治疗癌症的抗癌剂，特别是在个体不完全手术切除原发性肿瘤后的任何残留癌症。

    Tissue Inhibitor of Metalloproteinases (Timp) Linked to Glycosylphosphatidylinositol (Gpi) - Anchors for Treatment of Cancer and Skin Lesions
    10.
    发明申请
    Tissue Inhibitor of Metalloproteinases (Timp) Linked to Glycosylphosphatidylinositol (Gpi) - Anchors for Treatment of Cancer and Skin Lesions 有权
    与糖基磷脂酰肌醇（Gpi）相关的金属蛋白酶（Timp）组织抑制剂 - 用于治疗癌症和皮肤病变的锚点

    公开(公告)号：US20110105407A1

    公开(公告)日：2011-05-05

    申请号：US11992213

    申请日：2006-09-20

    申请人： Ralf Huss ,  Peter Jon Nelson

    发明人： Ralf Huss ,  Peter Jon Nelson

    IPC分类号： A61K38/57 ,  C07K14/81 ,  C07H21/04 ,  C12N15/63 ,  C12N5/10 ,  A61P35/00

    CPC分类号： A61K38/57 ,  A61K38/1709 ,  A61K47/544 ,  A61K47/549 ,  A61K47/62 ,  C07K14/8146

    摘要： The present invention relates to fusion constructs of glycosylphosphatidylinositol (GPI)-anchored tissue inhibitors of metalloproteinases (TIMPs) and their use for the treatment of cancer and in regenerative medicine. By this approach, the GPI-anchored TIMP proteins are incorporated into the surface membrane of tumor cells and render tumor cells sensitive to FAS-induced apoptosis. Furthermore, the fusion constructs of the present invention are effective agents useful in wound healing applications. In one embodiment, the TIMP is linked to mucin followed by GPI in order to enhance surface presentation. The use of GPI to link TIMP renders the resulting fusion protein particularly useful as an anti-cancer agent for the treatment of cancer, and, in particular, any residual cancer following an incomplete surgical resection of primary tumors in an individual.

    摘要翻译： 本发明涉及糖基磷脂酰肌醇（GPI） - 金属蛋白酶组织抑制剂（TIMP）的融合构建体及其在再生医学中的应用。 通过这种方法，GPI锚定的TIMP蛋白被并入肿瘤细胞的表面膜，并使肿瘤细胞对FAS诱导的细胞凋亡敏感。 此外，本发明的融合构建体是可用于伤口愈合应用的有效试剂。 在一个实施方案中，TIMP与粘蛋白连接，然后与GPI连接，以增强表面表达。 使用GPI连接TIMP使所得到的融合蛋白特别可用作治疗癌症的抗癌剂，特别是在个体不完全手术切除原发性肿瘤后的任何残留癌症。