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    Regulatory T cell mediator proteins and uses thereof
    2.
    发明授权
    Regulatory T cell mediator proteins and uses thereof 有权
    调节性T细胞介质蛋白及其用途

    公开(公告)号：US08501915B2

    公开(公告)日：2013-08-06

    申请号：US13546098

    申请日：2012-07-11

    申请人： Randolph J. Noelle ,  Li Wang

    发明人： Randolph J. Noelle ,  Li Wang

    IPC分类号： C07K16/00

    CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

    摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.

    摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞及其使用方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化。

    Compositions and methods for producing adaptive regulatory T cells
    4.
    发明授权
    Compositions and methods for producing adaptive regulatory T cells 有权
    用于生产适应性调节性T细胞的组合物和方法

    公开(公告)号：US08415154B2

    公开(公告)日：2013-04-09

    申请号：US12601682

    申请日：2008-05-29

    申请人： Randolph J. Noelle

    发明人： Randolph J. Noelle

    IPC分类号： C12N5/00

    CPC分类号： C12N5/0637 ,  A61K39/001 ,  A61K2035/122 ,  C12N5/0636 ,  C12N2501/385

    摘要： The present invention relates to a method for producing adaptive regulatory T cells from effector T cells by contacting the effector T cells with retinoic acid. Adaptive regulatory T cells produced by this method are Foxp3+, home to the gut, and are refractory to reversion in vivo. As such, such cells find application in the treatment of autoimmune disease and facilitating transplantation tolerance.

    摘要翻译： 本发明涉及通过使效应T细胞与视黄酸接触来从效应T细胞产生适应性调节性T细胞的方法。 通过该方法产生的适应性调节性T细胞是肠道归巢的Foxp3 +，并且在体内不可逆转。 因此，这样的细胞可用于治疗自身免疫性疾病并促进移植耐受。

    Regulatory T cell mediator proteins and uses thereof
    5.
    发明授权
    Regulatory T cell mediator proteins and uses thereof 有权
    调节性T细胞介质蛋白及其用途

    公开(公告)号：US08231872B2

    公开(公告)日：2012-07-31

    申请号：US12732371

    申请日：2010-03-26

    申请人： Randolph J. Noelle ,  Li Wang

    发明人： Randolph J. Noelle ,  Li Wang

    IPC分类号： A61K39/395

    CPC分类号： C07K16/2827 ,  A61K38/00 ,  A61K2039/505 ,  C07K14/70596 ,  C07K2319/00 ,  C07K2319/30 ,  G01N33/505 ,  Y02A50/412 ,  Y02A50/423

    摘要： The present invention relates to novel regulatory T cell proteins. One protein, designated PD-L3, resembles members of the PD-L1 family, and co-stimulates αCD3 proliferation of T cells in vitro. A second, TNF-like, protein has also been identified as being upregulated upon αCD3/αGITR stimulation. This protein has been designated Treg-sTNF. Proteins, antibodies, activated T cells and methods for using the same are disclosed.In particular methods of using these proteins and compounds, preferably antibodies, which bind or modulate (agonize or antagonize) the activity of these proteins, as immune modulators and for the treatment of cancer, autoimmune disease, allergy, infection and inflammatory conditions, e.g. multiple sclerosis is disclosed.

    摘要翻译： 本发明涉及新型调节性T细胞蛋白。 称为PD-L3的一种蛋白质类似于PD-L1家族的成员，并且在体外共同刺激T细胞的αCD3增殖。 第二种TNF样蛋白也被鉴定为在αCD3/αGITR刺激下上调。 该蛋白质已被命名为Treg-sTNF。 公开了蛋白质，抗体，活化的T细胞和使用它们的方法。 特别是使用这些蛋白质和化合物（优选抗体）的方法，其结合或调节（激动或拮抗）这些蛋白质的活性，作为免疫调节剂和用于治疗癌症，自身免疫疾病，变态反应，感染和炎性病症，例如， 公开了多发性硬化。

    Methods for reducing T cell responsiveness to an autoantigen with anti-gp39 antibodies and antigen presenting cells
    7.
    发明授权
    Methods for reducing T cell responsiveness to an autoantigen with anti-gp39 antibodies and antigen presenting cells 有权
    用抗Gp39抗体和抗原呈递细胞降低T细胞对自身抗原反应性的方法

    公开(公告)号：US07722874B2

    公开(公告)日：2010-05-25

    申请号：US09164568

    申请日：1998-10-01

    申请人： Randolph J. Noelle ,  Teresa M. Foy ,  Fiona H. Durie

    发明人： Randolph J. Noelle ,  Teresa M. Foy ,  Fiona H. Durie

    IPC分类号： A61K39/395 ,  A61K35/26 ,  A61K35/28

    CPC分类号： C07K14/70578 ,  A61K38/00 ,  A61K2039/505 ,  A61K2039/57 ,  C07K16/2875 ,  C07K19/00 ,  C07K2317/24 ,  C07K2317/73 ,  C07K2319/00 ,  G01N33/6854

    摘要： Methods for inducing antigen-specific T cell tolerance are disclosed. The methods involve contacting a T cell with: 1) a cell which presents antigen to the T cell, wherein a ligand on the cell interacts with a receptor on the surface of the T cell which mediates contact-dependent helper effector function; and 2) an antagonist of the receptor on the surface of the T cell which inhibits interaction of the ligand on the antigen presenting cell with the receptor on the T cell. In a preferred embodiment, the cell which presents antigen to the T cell is a B cell and the receptor on the surface of the T cell which mediates contact-dependent helper effector function is gp39. Preferably, the antagonist is an anti-gp39 antibody or a soluble gp39 ligand (e.g., soluble CD40). The methods of the invention can be used to induce T cell tolerance to a soluble antigen or to an allogeneic cell. The methods of the invention can also be used to induce tolerance in cases of bone marrow transplantation and other organ transplants and to inhibit graft-versus-host disease.

    摘要翻译： 公开了诱导抗原特异性T细胞耐受性的方法。 所述方法包括使T细胞接触：1）向T细胞呈递抗原的细胞，其中细胞上的配体与介导接触依赖性辅助效应子功能的T细胞表面上的受体相互作用; 和2）T细胞表面上的受体拮抗剂，其抑制抗原呈递细胞上的配体与T细胞上的受体的相互作用。 在优选的实施方案中，向T细胞呈递抗原的细胞是B细胞，介导接触依赖性辅助效应子功能的T细胞表面上的受体是gp39。 优选地，拮抗剂是抗gp39抗体或可溶性gp39配体（例如可溶性CD40）。 本发明的方法可用于诱导对可溶性抗原或同种异体细胞的T细胞耐受性。 本发明的方法还可用于在骨髓移植和其他器官移植的情况下诱导耐受性并抑制移植物抗宿主病。

    VISTA MODULATORS FOR DIAGNOSIS AND TREATMENT OF CANCER
    10.
    发明申请
    VISTA MODULATORS FOR DIAGNOSIS AND TREATMENT OF CANCER 有权

    公开(公告)号：US20140341920A1

    公开(公告)日：2014-11-20

    申请号：US14158531

    申请日：2014-01-17

    申请人： Randolph J. NOELLE

    发明人： Randolph J. NOELLE

    IPC分类号： C07K16/28

    CPC分类号： C07K16/2827 ,  A61K2039/505 ,  C07K14/70532 ,  C07K16/2803 ,  C07K2317/76

    摘要： The present disclosure relates to compositions and therapeutic methods for activating an immune response in a patient in need thereof. In a preferred embodiment, the subject methods and compositions are able to antagonize the activity of VISTA, a naturally occurring “checkpoint” protein which contributes to immune tolerance, optionally in combination with an antagonist of a second checkpoint pathway such as PD-1. For example, such methods and compositions may be suitable for preventing and treating colon cancer or another cancer. An exemplary VISTA antagonist, specifically, an anti-VISTA antibody, is demonstrated herein to activate an immune response against cancer cells in vitro and in vivo, thereby conferring protective anti-tumor immunity which decreased tumor burden. Additionally, an additive benefit was observed when a VISTA antagonist was used in combination with a second checkpoint protein antagonist, specifically, an antibody against PD-1 ligand (PD-L1).