公开(公告)号：WO2017132420A1

公开(公告)日：2017-08-03

申请号：PCT/US2017/015198

申请日：2017-01-26

申请人： THE METHODIST HOSPITAL

发明人： LI, Xian Chang ,  FAN, Yihui

IPC分类号： A61K38/17 ,  A61K48/00 ,  A61K9/127 ,  A61K9/51

CPC分类号： A61K38/465 ,  A01K2207/12 ,  A01K2227/105 ,  A01K2267/0331 ,  C12N9/16 ,  C12N9/22

摘要： Disclosed are methods for determining the metastatic potential of mammalian tumors and other cancers. Also disclosed are methods for altering the metastatic potential of mammalian cancers, by a) directly or indirectly increasing the level of Regnase peptide or polypeptide; b) selectively increasing the activity or specificity of Regnase peptide or polypeptide; c) selectively increasing the amount or stability of Regnase-specific mRNA; or d) selectively inhibiting one or more negative effectors of Regnase within a cancer cell in an amount and for a time effective to reduce, delay, retard, or prevent subsequent metastasis of the cancer within the body of a mammal. Also disclosed are methods for predicting cancer cell metastasis, and methods for determining the likelihood of patient outcomes by quantitating Regnase-specific expression or activity thereby providing a biomarker for determining the metastatic potential of a given cancer.

摘要翻译： 公开了用于确定哺乳动物肿瘤和其他癌症的转移潜能的方法。 还公开了通过以下方法来改变哺乳动物癌症的转移潜能的方法：a）直接或间接增加雷珠朊酶肽或多肽的水平; b）选择性地增加Regnase肽或多肽的活性或特异性; c）选择性增加Regnase特异性mRNA的量或稳定性; 或d）选择性抑制癌细胞内Regnase的一种或多种负效应物，其量和时间有效减少，延迟，延迟或预防哺乳动物体内癌症的后续转移。 还公开了用于预测癌细胞转移的方法，以及通过定量Regnase特异性表达或活性来确定患者结果的可能性的方法，从而提供用于确定给定癌症的转移潜能的生物标志物。

公开(公告)号：WO2019200216A1

公开(公告)日：2019-10-17

申请号：PCT/US2019/027162

申请日：2019-04-12

申请人： THE METHODIST HOSPITAL SYSTEM

发明人： CHEN, Wenhao ,  LI, Xian Chang

IPC分类号： A61K31/517 ,  A61K31/551 ,  A61K31/5513 ,  A61K31/7088 ,  A61K45/06 ,  C07H21/02

摘要： Disclosed are methods and compositions for inhibiting IRF4 in T-cells, thereby improving transplant outcomes or treating an autoimmune disease such as a myelination disorder. Thus, disclosed are methods to improve a transplant outcome in a recipient of a transplant comprising inhibiting IRF4 in T-cells of the recipient, thereby improving the transplant outcome. In some embodiments, IRF4 can be inhibited by administering an IRF4 inhibitor (e.g., trametinib or anti-IRF4 siRNA), and/or by adoptive transfer of T-cells having IRF4 inhibition. In some embodiments, the T-cells are CD4+ Tcells, and the infiltration thereof into a transplant can be reduced. Also disclosed are methods of treating a subject with a myelination disorder (e.g., multiple sclerosis or encephalomyelitis) comprising inhibiting IRF4.

公开(公告)号：WO2019168914A1

公开(公告)日：2019-09-06

申请号：PCT/US2019/019745

申请日：2019-02-27

申请人： THE METHODIST HOSPITAL SYSTEM

发明人： CHEN, Wenhao ,  LI, Xian Chang

IPC分类号： A61K35/17 ,  A61K38/21 ,  A61K45/00 ,  A61K48/00 ,  A61P35/00 ,  C07K14/725 ,  C12N5/0783 ,  C12N15/63

摘要： Methods to treat cancer in a subject comprising administering to the subject a therapeutically effective amount of T-cells of the subject having increased IRF4 polypeptide expression compared to a control are disclosed. Also disclosed are methods of increasing tumor reactivity of a T-cell by increasing IRF4 polypeptide expression, and methods to predict the likelihood that a subject having cancer will respond therapeutically to administered T-cells having increased IRF4 polypeptide expression. Also disclosed are compositions comprising a T-cell and a viral vector encoding an IRF4 polypeptide. The compositions are methods are useful for treating numerous cancers in which higher level expression of IRF4 in T-cells would be beneficial. In some embodiments, activated tumorspecific T-cells having increased IRF4 expression have greater infiltration in tumors and enhanced local immunological responses.

公开(公告)号：WO2017165614A1

公开(公告)日：2017-09-28

申请号：PCT/US2017/023756

申请日：2017-03-23

申请人： THE METHODIST HOSPITAL SYSTEM

发明人： LI, Xian Chang ,  GHOBRIAL, Rafik Mark ,  MYSORE, Krupa Ramaprasad

IPC分类号： A61B5/117 ,  C12N15/09 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/74 ,  G06F19/22

摘要： Disclosed herein are methods for scoring a patient on a liver transplant list, methods of performing a liver transplant, methods of determining expected post-transplant mortality in a subject, and methods of determining expected sepsis. The disclosed methods can be used to avoid futile transplantation, avoid wasting organs, and promote efficient management of organ placement. These methods involve assaying a sample from the subject for T cell receptor (TCR) repertoire.

摘要翻译： 本文公开了用于对肝脏移植名单上的患者进行评分的方法，进行肝脏移植的方法，确定受试者的预期移植后死亡率的方法以及确定预期败血症的方法。 所公开的方法可用于避免无效移植，避免器官浪费，并促进器官放置的有效管理。 这些方法涉及测定受试者的样品中的T细胞受体（TCR）库。