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公开(公告)号:US20220142948A1
公开(公告)日:2022-05-12
申请号:US17440282
申请日:2020-03-18
申请人: The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc. , The Regents of the University of California
发明人: Aviv Regev , Chao Wang , Vijay K. Kuchroo , Nir Yosef , Allon Wagner , Johannes Fessler
IPC分类号: A61K31/132 , C12N5/0783 , C12N9/02 , C12N9/10 , C12N9/88 , C12N15/11
摘要: The subject matter disclosed herein is generally directed to modulation of Th17 differentiation and pathogenicity by use of metabolic targets. The metabolic targets are the molecules of the polyamine pathway or glycolysis pathway. Modulation of the polyamine pathway can shift Th17 pathogenicity and shift the transcriptome of Th17 cells to a Treg or Th1 transcriptome. The polyamine analogue DFMO can be used to modulate an inflammatory response. Inhibitors of enzymes in the glycolysis pathway can shift Th17 pathogenicity.
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公开(公告)号:US11186825B2
公开(公告)日:2021-11-30
申请号:US15966244
申请日:2018-04-30
申请人: The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
发明人: Aviv Regev , Ana Carrizosa Anderson , Le Cong , Vijay K. Kuchroo , Meromit Singer , Chao Wang
IPC分类号: C12N5/0783 , A61K35/17 , A61K39/00 , C12Q1/6881 , C12Q1/6886 , C07K14/00 , C07K14/47 , G01N33/50 , A61K45/06 , C12N15/10 , C12Q1/6883
摘要: The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, POU2AF1 modulation is provided for use as a marker, marker signature and molecular target. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.
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3.
公开(公告)号:US20210102166A1
公开(公告)日:2021-04-08
申请号:US17063617
申请日:2020-10-05
申请人: Dana-Farber Cancer Institute, Inc. , The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
IPC分类号: C12N5/0783 , A61K35/17 , C12Q1/6881 , G01N33/50 , A61P37/06
摘要: The subject matter disclosed herein is generally directed to tissue specific modulation of Th17 differentiation and pathogenicity by targeting tissue specific Th17 gene programs and gene targets. The tissue specific modulation may be used therapeutically to treat a disease or condition in the tissue where it arises. The subject matter disclosed herein is also directed to detecting tissue specific Th17 cells for diagnostic and therapeutic methods.
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4.
公开(公告)号:US20190100801A1
公开(公告)日:2019-04-04
申请号:US15966324
申请日:2018-04-30
申请人: The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
发明人: Aviv Regev , Ana Carrizosa Anderson , Le Cong , Vijay K. Kuchroo , Meromit Singer , Chao Wang
IPC分类号: C12Q1/6881 , C12Q1/6853 , C12Q1/686 , C12Q1/6806
摘要: The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.
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公开(公告)号:US11427869B2
公开(公告)日:2022-08-30
申请号:US15687089
申请日:2017-08-25
申请人: THE BROAD INSTITUTE, INC. , MASSACHUSETTS INSTITUTE OF TECHNOLOGY , PRESIDENT AND FELLOWS OF HARVARD COLLEGE , THE BRIGHAM AND WOMEN'S HOSPITAL, INC. , THE REGENTS OF THE UNIVERSITY OF CALIFORNIA
发明人: Aviv Regev , Vijay K. Kuchroo , Jellert Gaublomme , Youjin Lee , Chao Wang , Nir Yosef , Hongkun Park , James Kaminski
IPC分类号: C12Q1/6883 , C12Q1/6881 , G01N33/50
摘要: This invention relates generally to compositions and methods for identifying the regulatory network that modulates, controls or otherwise influences T cell balance, for example, Th17 cell differentiation, maintenance and/or function, as well compositions and methods for exploiting the regulatory network that modulates, controls or otherwise influences T cell balance in a variety of therapeutic and/or diagnostic indications. This invention also relates generally to identifying and exploiting target genes and/or target gene products that modulate, control or otherwise influence T cell balance in a variety of therapeutic and/or diagnostic indications.
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公开(公告)号:US20210317186A1
公开(公告)日:2021-10-14
申请号:US17226506
申请日:2021-04-09
申请人: The Brigham and Women's Hospital, Inc. , The Broad Institute, Inc. , Massachusetts Institute of Technology
发明人: Vijay K. Kuchroo , Chao Wang , Aviv Regev , Karthik Shekhar
IPC分类号: C07K14/705 , A61K38/20 , A61K38/17 , A61P37/00 , A61P1/00 , A61P35/00 , A61K39/395 , A61K45/06 , C07K14/54 , C07K16/24 , C07K16/28 , C12N15/113
摘要: Described herein are methods for suppressing an immune response in a subject, e.g., a subject with an autoimmune disease, by administering to the subject a therapeutically effective amount of recombinant CD5L, CD5L homodimers and/or CD5L:p40 heterodimers, or nucleic acids encoding any of these. Also described are methods for enhancing an immune response in a subject, e.g., a subject with cancer, infection, or an immune deficiency, by administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds specifically to CD5L, D5L homodimers and/or CD5L:p40 heterodimers, and inhibits their binding to the IL-23 receptor, or inhibits formation of the CD5L homodimer and/or CD5L:p40 heterodimer, or inhibitory nucleic acids that target CD5L and/or p40.
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公开(公告)号:US20210130438A1
公开(公告)日:2021-05-06
申请号:US17083235
申请日:2020-10-28
申请人: The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
IPC分类号: C07K14/715 , C12N15/90 , C12N5/0783 , A61K35/17 , C07K16/28 , A61K39/395 , C12Q1/6886 , G01N33/50 , A61P35/00
摘要: The present invention provides novel pan-cancer T cell exhaustion regulators. CXCR6 expressed in CD8+ T cells was specifically identified as regulating anti-tumor immunity. Modulating CXCR6-CXCL16 interaction is useful in modulating anti-tumor immunity. The identified genes may be modulated in T cells for use in adoptive cell transfer. The identified genes may be modulated in vivo.
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公开(公告)号:US11180730B2
公开(公告)日:2021-11-23
申请号:US15966290
申请日:2018-04-30
申请人: The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
发明人: Aviv Regev , Ana Carrizosa Anderson , Le Cong , Vijay K. Kuchroo , Meromit Singer , Chao Wang
IPC分类号: C12N5/0783 , A61K35/17 , A61K39/00 , G01N33/50 , A61K45/06 , C12N15/10 , C12Q1/6883
摘要: The present invention provides markers, marker signatures and molecular targets that correlate with dysfunction of immune cells and are advantageously independent of the immune cell activation status. The present markers, marker signatures and molecular targets provide for new ways to evaluate and modulate immune responses. Specifically, GATA3 and/or FOXO1 modulation are provided for use as markers, marker signatures and molecular targets. Therapeutic methods are also provided to treat a patient in need thereof who would benefit from an increased immune response.
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公开(公告)号:US11001622B2
公开(公告)日:2021-05-11
申请号:US15777054
申请日:2016-11-17
申请人: The Brigham and Women's Hospital, Inc. , The Broad Institute, Inc. , Massachusetts Institute of Technology
发明人: Vijay K. Kuchroo , Chao Wang , Aviv Regev , Karthik Shekhar
IPC分类号: A61K38/00 , C07K14/705 , A61K38/20 , A61K38/17 , A61P37/00 , A61P1/00 , A61P35/00 , A61K39/395 , A61K45/06 , C07K14/54 , C07K16/24 , C07K16/28 , C12N15/113 , A61K39/00
摘要: Described herein are methods for suppressing an immune response in a subject, e.g., a subject with an autoimmune disease, by administering to the subject a therapeutically effective amount of recombinant CD5L, CD5L homodimers and/or CD5L:p40 heterodimers, or nucleic acids encoding any of these. Also described are methods for enhancing an immune response in a subject, e.g., a subject with cancer, infection, or an immune deficiency, by administering to the subject a therapeutically effective amount of an antibody or antigen-binding fragment thereof that binds specifically to CD5L, D5L homodimers and/or CD5L:p40 heterodimers, and inhibits their binding to the IL-23 receptor, or inhibits formation of the CD5L homodimer and/or CD5L:p40 heterodimer, or inhibitory nucleic acids that target CD5L and/or p40.
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公开(公告)号:US20210121530A1
公开(公告)日:2021-04-29
申请号:US16497105
申请日:2018-03-23
申请人: The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
发明人: Antonia Wallrapp , Samantha J. Riesenfeld , Patrick R. Burkett , Monika S. Kowalczyk , Aviv Regev , Vijay K. Kuchroo
IPC分类号: A61K38/20 , A61K38/22 , A61K9/00 , C12Q1/6883 , A61P37/08
摘要: Computational and functional analysis identified the neuropeptide receptor Nmur1 as selectively expressed on Type 2 innate lymphoid cells (ILC2s). While both IL-33 and IL-25 promote ILC activation in vivo, IL-33 induces robust ILC proliferation, whereas ILCs activated with IL-25 do not proliferate as robustly and up-regulate Nmur1 expression. Treatment with neuromedin U (NMU), the neuropeptide ligand of Nmur1, had little effect on its own. Co-administration of IL-25 with NMU, however, dramatically amplified allergic lung inflammation and induced the proliferation and expansion of specific ILC2 subsets, characterized by a molecular signature unique to pro-inflammatory ILC2s. The results demonstrate that Nmur1 signaling strongly modulates IL-25-mediated ILC2 responses, resulting in highly proliferative pro-inflammatory ILCs, and highlights the importance of neuro-immune crosstalk in allergic inflammatory responses at mucosal surfaces.
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