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    Immunosuppression By Blocking T Cell Co-Stimulation Signal 2 (B7/CD28 Interaction)
    2.
    发明申请
    Immunosuppression By Blocking T Cell Co-Stimulation Signal 2 (B7/CD28 Interaction) 有权
    免疫抑制通过阻断T细胞共刺激信号2（B7 / CD28相互作用）

    公开(公告)号：US20130078266A1

    公开(公告)日：2013-03-28

    申请号：US13316791

    申请日：2011-12-12

    申请人： Robert Ian Lechler ,  Anthony Dorling

    发明人： Robert Ian Lechler ,  Anthony Dorling

    IPC分类号： C07K14/705

    CPC分类号： C07K14/70596 ,  A01K67/0275 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/001 ,  A61K48/00 ,  A61K2039/5154 ,  A61K2039/5156 ,  C07K14/70521 ,  C07K14/70532 ,  C07K16/2818 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30

    摘要： The invention provides methods for inhibiting T-cell mediated rejection of a xenotransplanted organ by blocking the delivery of co-stimulatory signal 2 (the B7/CD28 interaction) prevent the activation of xenoreactive T-cells in the recipient. In a first aspect, co-stimulation is prevented by administration to the organ recipient of a soluble form of CTLA-4 from the xenogeneic donor organism. In a second aspect, co-stimulation is antagonised by expressing a ligand for CTLA-4 on the xenogeneic donor cells. In a third aspect, co-stimulation is prevented by expressing recipient organism MHC class II on the surface of the cells of the xenogeneic donor organ.

    摘要翻译： 本发明提供了通过阻止共刺激信号2（B7 / CD28相互作用）的传递来阻止异种移植器官的T细胞介导的排斥来防止接受者中异反应性T细胞的活化的方法。 在第一方面，通过向来自异种供体生物体的可溶形式的CTLA-4的器官受体施用来预防共刺激。 在第二方面，通过在异种供体细胞上表达CTLA-4的配体来拮抗共刺激。 在第三方面，通过在异种供体器官的细胞表面上表达受体生物体MHC II类来预防共刺激。

    Immunosuppression by blocking T cell co-stimulation signal 2 (B7/CD28 interaction)
    4.
    发明申请
    Immunosuppression by blocking T cell co-stimulation signal 2 (B7/CD28 interaction) 有权
    通过阻断T细胞共刺激信号2的免疫抑制（B7 / CD28相互作用）

    公开(公告)号：US20100146648A1

    公开(公告)日：2010-06-10

    申请号：US12231608

    申请日：2008-09-04

    申请人： Robert Ian Lechler ,  Anthony Dorling

    发明人： Robert Ian Lechler ,  Anthony Dorling

    IPC分类号： A01K67/00 ,  C07H21/04 ,  A61K38/16 ,  A61K39/00 ,  C12N5/071 ,  A61K45/00 ,  A61P37/06

    CPC分类号： C07K14/70596 ,  A01K67/0275 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/001 ,  A61K48/00 ,  A61K2039/5154 ,  A61K2039/5156 ,  C07K14/70521 ,  C07K14/70532 ,  C07K16/2818 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30

    摘要： The invention provides means and methods for inhibiting T-cell mediated rejection of a xenotransplanted organ by blocking the delivery of co-stimulatory signal 2 (the B7/CD28 interaction) in order to prevent the activation of xenoreactive T-cells in the recipient. In a first aspect, co-stimulation is prevented by administration to the organ recipient of a soluble form of CTLA-4 from the xenogeneic donor organism. This preferentially binds B7 on the xenograft and blocks the interaction between B7 on the xenogeneic donor cells and CD28 on recipient T-cells. In a second aspect, co-stimulation is antagonised by expressing a ligand for CTLA-4 on the xenogeneic donor cells. This ligand binds to CTLA-4 on activated T-cells of the recipient and antagonises signal 2. In a third aspect, co-stimulation is prevented by expressing recipient organism MHC class II on the surface of the cells of the xenogeneic donor organ. The donor cells are thus able to present xenoantigens to a recipient T-cell in the context of self-MHC class II. If the donor cells do not express B7, or if B7 is blocked, the xenoreactive recipient T-cell becomes anergic.

    摘要翻译： 本发明提供了通过阻止共刺激信号2（B7 / CD28相互作用）的递送来抑制异种移植器官的T细胞介导的排斥的方法和方法，以便防止接受者中异反应性T细胞的活化。 在第一方面，通过向来自异种供体生物体的可溶形式的CTLA-4的器官受体施用来预防共刺激。 这优先结合异种移植物上的B7并阻断异种供体细胞上的B7与受体T细胞上的CD28之间的相互作用。 在第二方面，通过在异种供体细胞上表达CTLA-4的配体来拮抗共刺激。 该配体在受体的活化T细胞上结合CTLA-4并拮抗信号2.在第三方面，通过在异种供体器官的细胞表面上表达受体生物体MHC II类来预防共刺激。 因此，供体细胞能够在自身MHC II类的上下文中向受体T细胞呈递异种抗原。 如果供体细胞不表达B7，或者如果B7被阻断，则异种活化受体T细胞变得无能。

    Porcine CTLA-4 for xenograft-specific immunosuppression
    5.
    发明授权
    Porcine CTLA-4 for xenograft-specific immunosuppression 有权
    猪CTLA-4用于异种移植物特异性免疫抑制

    公开(公告)号：US07432344B1

    公开(公告)日：2008-10-07

    申请号：US09674462

    申请日：1999-04-30

    申请人： Robert Ian Lechler ,  Anthony Dorling

    发明人： Robert Ian Lechler ,  Anthony Dorling

    IPC分类号： C07K14/46 ,  C07K14/705 ,  C07K14/725 ,  C07K16/46

    CPC分类号： C07K14/70596 ,  A01K67/0275 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/001 ,  A61K48/00 ,  A61K2039/5154 ,  A61K2039/5156 ,  C07K14/70521 ,  C07K14/70532 ,  C07K16/2818 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30

    摘要： The invention provides compositions and methods for inhibiting T-cell mediated rejection of a xenotransplanted organ by blocking the delivery of co-stimulatory signal 2 (the B7/CD28 interaction) in order to prevent the activation of xenoreactive T-cells in the recipient. In a first aspect, co-stimulation is prevented by administration to the organ recipient of a soluble form of CTLA-4 from the xenogeneic donor organism. This preferentially binds B7 on the xenograft and blocks the interaction between B7 on the xenogeneic donor cells and CD28 on recipient T-cells. In a second aspect, co-stimulation is antagonised by expressing a ligand for CTLA-4 on the xenogeneic donor cells. This ligand binds to CTLA-4 on activated T-cells of the recipient and antagonizes signal 2. In a third aspect, co-stimulation is prevented by expressing recipient organism MHC class II on the surface of the cells of the xenogeneic donor organ. The donor cells are thus able to present xenoantigens to a recipient T-cell in the context of self-MHC class II. If the donor cells do not express B7, or if B7 is blocked, the xenoreactive recipient T-cell becomes anergic.

    摘要翻译： 本发明提供了通过阻止共刺激信号2（B7 / CD28相互作用）的递送来抑制异种移植器官的T细胞介导的排斥的组合物和方法，以便防止接受者中异反应性T细胞的活化。 在第一方面，通过向来自异种供体生物体的可溶形式的CTLA-4的器官受体施用来预防共刺激。 这优先结合异种移植物上的B7并阻断异种供体细胞上的B7与受体T细胞上的CD28之间的相互作用。 在第二方面，通过在异种供体细胞上表达CTLA-4的配体来拮抗共刺激。 该配体在受体的活化T细胞上结合CTLA-4并拮抗信号2.在第三方面，通过在异种供体器官的细胞表面上表达受体生物体MHC II类来预防共刺激。 因此，供体细胞能够在自身MHC II类的上下文中向受体T细胞呈递异种抗原。 如果供体细胞不表达B7，或者如果B7被阻断，则异种活化受体T细胞变得无能。

    Porcine CTLA-4 for xenograft-specific immunosuppression
    7.
    发明授权
    Porcine CTLA-4 for xenograft-specific immunosuppression 有权
    猪CTLA-4用于异种移植物特异性免疫抑制

    公开(公告)号：US08097598B2

    公开(公告)日：2012-01-17

    申请号：US12231608

    申请日：2008-09-04

    申请人： Robert Ian Lechler ,  Anthony Dorling

    发明人： Robert Ian Lechler ,  Anthony Dorling

    IPC分类号： A61K48/00

    CPC分类号： C07K14/70596 ,  A01K67/0275 ,  A01K2217/05 ,  A61K38/00 ,  A61K39/001 ,  A61K48/00 ,  A61K2039/5154 ,  A61K2039/5156 ,  C07K14/70521 ,  C07K14/70532 ,  C07K16/2818 ,  C07K2317/622 ,  C07K2319/00 ,  C07K2319/30

    摘要： The invention provides means and methods for inhibiting T-cell mediated rejection of a xenotransplanted organ by blocking the delivery of co-stimulatory signal 2 (the B7/CD28 interaction) in order to prevent the activation of xenoreactive T-cells in the recipient. In a first aspect, co-stimulation is prevented by administration to the organ recipient of a soluble form of CTLA-4 from the xenogeneic donor organism. This preferentially binds B7 on the xenograft and blocks the interaction between B7 on the xenogeneic donor cells and CD28 on recipient T-cells. In a second aspect, co-stimulation is antagonized by expressing a ligand for CTLA-4 on the xenogeneic donor cells. This ligand binds to CTLA-4 on activated T-cells of the recipient and antagonizes signal 2. In a third aspect, co-stimulation is prevented by expressing recipient organism MHC class II on the surface of the cells of the xenogeneic donor organ. The donor cells are thus able to present xenoantigens to a recipient T-cell in the context of self-MHC class II. If the donor cells do not express B7, or if B7 is blocked, the xenoreactive recipient T-cell becomes anergic.

    摘要翻译： 本发明提供了通过阻止共刺激信号2（B7 / CD28相互作用）的递送来抑制异种移植器官的T细胞介导的排斥的方法和方法，以便防止接受者中异反应性T细胞的活化。 在第一方面，通过向来自异种供体生物体的可溶形式的CTLA-4的器官受体施用来预防共刺激。 这优先结合异种移植物上的B7并阻断异种供体细胞上的B7与受体T细胞上的CD28之间的相互作用。 在第二方面，通过在异种供体细胞上表达CTLA-4的配体来拮抗共刺激。 该配体在受体的活化T细胞上结合CTLA-4并拮抗信号2.在第三方面，通过在异种供体器官的细胞表面上表达受体生物体MHC II类来预防共刺激。 因此，供体细胞能够在自身MHC II类的上下文中向受体T细胞呈递异种抗原。 如果供体细胞不表达B7，或者如果B7被阻断，则异种活化受体T细胞变得无能。