公开(公告)号：US20110130303A1

公开(公告)日：2011-06-02

申请号：US13000931

申请日：2009-07-03

申请人： Alberto Sanchez Fueyo ,  Juan José Lozano Salvatella

发明人： Alberto Sanchez Fueyo ,  Juan José Lozano Salvatella

IPC分类号： C40B30/04 ,  G01N33/53 ,  C40B30/00 ,  C12Q1/68 ,  G01N33/50 ,  C40B40/00 ,  C40B40/06 ,  C40B40/10 ,  C12M1/34

CPC分类号： C12Q1/6881 ,  C12Q2600/158 ,  G01N33/6893 ,  G01N2800/245 ,  G01N2800/52

摘要： In vitro diagnosis/prognosis method and kit, for assessment of tolerance in liver transplantation. The present invention refers to the study of peripheral blood transcriptional patterns from 80 liver transplant recipients and 16 non-transplanted healthy individuals employing either oligonucleotide microarrays and/or quantitative real-time PCR to design a clinically applicable molecular test. This has resulted in the discovery and validation of several gene signatures comprising a modest number of genes capable of identifying tolerant and non-tolerant recipients with high accuracy. The marker genes are KLRF1, SLAMF7, NKG7, IL2RB, KLRB1, FANCG, GNPTAB, CLIC3, PSMD14, ALG8, CX3CR1, RGS 3. Multiple peripheral blood lymphocyte subsets contribute to the tolerance-associated transcriptional patterns with NK and γdelta T cells exerting a predominant influence. The invention concludes that transcriptional profiling of peripheral blood can be employed to identify liver transplant recipients who can discontinue immunosuppressive therapy and that innate immune cells are likely to play a major role in the maintenance of operational tolerance in liver transplantation.

摘要翻译： 体外诊断/预后方法和试剂盒，用于评估肝移植中的耐受性。 本发明涉及使用寡核苷酸微阵列和/或定量实时PCR从80个肝移植受体和16个非移植健康个体的外周血转录模式的研究来设计临床适用的分子测试。 这导致了几种基因特征的发现和验证，其包括能够以高精度识别耐受性和非耐受性受体的适度数量的基因。 标记基因是KLRF1，SLAMF7，NKG7，IL2RB，KLRB1，FANCG，GNPTAB，CLIC3，PSMD14，ALG8，CX3CR1，RGS 3.多个外周血淋巴细胞亚群有助于与NK和γdeltaT细胞发挥耐受相关的转录模式 主要影响。 本发明的结论是，可以使用外周血的转录谱来鉴定可以停止免疫抑制治疗的肝移植受体，并且先天免疫细胞可能在维持肝移植中的操作耐受中起主要作用。

公开(公告)号：US08329660B2

公开(公告)日：2012-12-11

申请号：US10958169

申请日：2004-10-04

申请人： Vijay K. Kuchroo ,  Terry Strom ,  Eugene K. Cha ,  Sumone Chakravarti ,  Catherine Sabatos ,  Chen Zhu ,  Xin Xiao Zheng ,  Alberto Sanchez-Fueyo

发明人： Vijay K. Kuchroo ,  Terry Strom ,  Eugene K. Cha ,  Sumone Chakravarti ,  Catherine Sabatos ,  Chen Zhu ,  Xin Xiao Zheng ,  Alberto Sanchez-Fueyo

IPC分类号： A61K39/395

CPC分类号： C07K16/18 ,  C07K14/4713 ,  C07K14/70503 ,  C07K16/28 ,  C07K2319/30 ,  G01N33/505

摘要： The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

摘要翻译： 本发明涉及分离的多肽和编码多肽的核酸，其包含tim-3 IgV结构域和tim-3细胞内结构域，其中所述多肽不包含tim-3粘蛋白结构域或tim-3跨膜结构域。 此外，本发明涉及调节受试者中的免疫应答的方法，包括向受试者施用治疗有效量的调节tim-3活性的药剂。 免疫反应包括但不限于免疫耐受性，移植耐受性，Th1应答和Th2应答。

公开(公告)号：US20100304987A1

公开(公告)日：2010-12-02

申请号：US12522120

申请日：2008-01-04

申请人： Alberto Sanchez Fueyo ,  Marc Martinez Llordella ,  Isabel Puig Pey ,  Antoni Rimola Castella ,  Juan Jose Lozano Salvatella

发明人： Alberto Sanchez Fueyo ,  Marc Martinez Llordella ,  Isabel Puig Pey ,  Antoni Rimola Castella ,  Juan Jose Lozano Salvatella

IPC分类号： C40B30/04 ,  C12Q1/68 ,  C40B40/06

CPC分类号： C12Q1/6883 ,  C12Q1/6881 ,  C12Q2600/106 ,  C12Q2600/158 ,  G01N2800/245

摘要： The long-term survival of transplanted grafts critically depends on the life-long administration of immunosuppressive drugs to prevent graft rejection. These drugs are very effective at preventing graft rejection, but they are also associated with severe side effects. Inventors have selected a set of genes whose expression characterizes the tolerant state in liver transplantation in humans. Based on the expression level profile of this set of genes, inventors provide a non-invasive method to assess diagnosis and/or prognosis of the tolerant state in liver transplantation in humans, and kits to perform it. These kits are simpler and cheaper than others based on a great number of genes, such as commercial microarrays with thousands of probes.

摘要翻译： 移植移植物的长期生存关键取决于免疫抑制药物的终身施用以防止移植物排斥。 这些药物在预防移植排斥反应方面非常有效，但也与严重的副作用有关。 发明人已经选择了一组基因，其表达在人类肝移植中表现为耐受状态。 基于这组基因的表达水平分布，发明人提供了非侵入性方法来评估人类肝移植中的耐受状态的诊断和/或预后，以及用于执行它的试剂盒。 基于许多基因，例如具有数千个探针的商业微阵列，这些试剂盒比其他试剂更简单和便宜。

公开(公告)号：US20050191721A1

公开(公告)日：2005-09-01

申请号：US10958169

申请日：2004-10-04

申请人： Vijay Kuchroo ,  Terry Strom ,  Eugene Cha ,  Sumone Chakravarti ,  Catherine Sabatos ,  Chen Zhu ,  Xin Zheng ,  Alberto Sanchez-Fueyo

发明人： Vijay Kuchroo ,  Terry Strom ,  Eugene Cha ,  Sumone Chakravarti ,  Catherine Sabatos ,  Chen Zhu ,  Xin Zheng ,  Alberto Sanchez-Fueyo

IPC分类号： C07H21/04 ,  C07K14/47 ,  C07K14/705 ,  C07K16/18 ,  C07K16/28 ,  C12N5/06

CPC分类号： C07K16/18 ,  C07K14/4713 ,  C07K14/70503 ,  C07K16/28 ,  C07K2319/30 ,  G01N33/505

摘要： The invention relates to isolated polypeptides and nucleic acids encoding polypeptides which comprise a tim-3 IgV domain and a tim-3 intracellular domain, wherein the polypeptides do not comprise a tim-3 mucin domain or a tim-3 transmembrane domain. In addition, the invention relates to methods of modulating immune responses in a subject, comprising administering to the subject a therapeutically effective amount of an agent that modulates tim-3 activity. Immune responses include, but are not limited to, immune tolerance, transplantation tolerance, Th1 responses and Th2 responses.

摘要翻译： 本发明涉及分离的多肽和编码多肽的核酸，其包含tim-3 IgV结构域和tim-3细胞内结构域，其中所述多肽不包含tim-3粘蛋白结构域或tim-3跨膜结构域。 此外，本发明涉及调节受试者中的免疫应答的方法，包括向受试者施用治疗有效量的调节tim-3活性的药剂。 免疫反应包括但不限于免疫耐受性，移植耐受性，Th1应答和Th2应答。