利索-全球专利检索

  1. 登录
  2. 注册

搜索结果

114 条记录 (耗时 0.066 秒)

    DETECTION MEANS, COMPOSITIONS AND METHODS FOR MODULATING SYNOVIAL SARCOMA CELLS
    5.
    发明申请
    DETECTION MEANS, COMPOSITIONS AND METHODS FOR MODULATING SYNOVIAL SARCOMA CELLS 有权

    公开(公告)号：US20220154282A1

    公开(公告)日：2022-05-19

    申请号：US17438051

    申请日：2020-03-12

    申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  The General Hospital Corporation

    发明人： Aviv Regev ,  Livnat Jerby-Arnon ,  Mario Suva ,  Nicolo Riggi

    IPC分类号： C12Q1/6886

    摘要： The present invention provides novel compositions and methods based on the discovery of the mechanisms and gene expression programs associated with synovial sarcoma. In particular, core oncogenic programs were expressed by a distinct subpopulation of malignant cells and associated with poor clinical outcome, a cell cycle program distinguished cycling from non-cycling cells, with cycling cells having a tendency to be poorly differentiated and indicative of increased risk of metastatic disease, and a (de)differentiation program that can identify poorly differentiated cells, the absence of which was prognostic of metastasis free survival. Methods of treatment include use of HDAC and CDK4/6 inhibitors to block oncogenic program to selectively target synovial sarcoma cells. Finally, macrophages and T cells can mimic the effect of SS18-SSX inhibition by secreting TNFa and IFNg, which allows for adoptive cell therapy to provide cells with increased expression of TNFa and IFNg.

    COMPOSITIONS AND METHODS FOR MODULATING CGRP SIGNALING TO REGULATE INTESTINAL INNATE LYMPHOID CELLS
    9.
    发明申请
    COMPOSITIONS AND METHODS FOR MODULATING CGRP SIGNALING TO REGULATE INTESTINAL INNATE LYMPHOID CELLS 有权

    公开(公告)号：US20220143148A1

    公开(公告)日：2022-05-12

    申请号：US17438972

    申请日：2020-03-13

    申请人： The Broad Institute, Inc. ,  Massachusetts Institute of Technology ,  The General Hospital Corporation

    发明人： Aviv Regev ,  Heping Xu ,  Jiarui Ding ,  Ramnik Xavier

    IPC分类号： A61K38/23 ,  A61P37/00 ,  C12N15/11 ,  C12N9/22

    摘要： The present invention provides novel compositions and methods based on the discovery of the mechanisms and gene expression programs associated with homeostatic ILC2s and proinflammatory ILC2s that drive tissue inflammation. Immune signaling abnormalities in the small intestine can trigger chronic type 2 inflammation. Applicants analyzed 58,067 immune cells from the mouse small intestine by single-cell RNA-seq at steady state and after induction of a type 2 inflammatory reaction to ovalbumin. Cell type composition and cell programs shifted in response to inflammation, especially in ILC2s. A key transcript in the inflammation-induced program in intestinal KLRG1+ILC2s was exon 5 of Calca, encoding the alpha-calcitonin gene-related peptide (a-CGRP). a-CGRP antagonized IL-25-induced activation of intestinal ILC2s and reduced their frequency in an ovalbumin reaction model. α-CGRP activated a cAMP response, which suppressed ILC2 proliferation. In homeostasis, α-CGRP was expressed by two subsets of ChAT+ enteric neurons, and genetic perturbation of α-CGRP increased the proportion of intestinal ILC2s and of Tuft cells. The results demonstrate that a-CGRP-mediated neuronal signaling suppresses ILC2 expansion and maintains type 2 immunity homeostasis.