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公开(公告)号：US20210047694A1
公开(公告)日：2021-02-18
申请号：US16995425
申请日：2020-08-17
申请人： The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc. , The General Hospital Corporation
发明人： Aviv Regev , Nir Hacohen , Vijay K. Kuchroo , Ana Carrizosa Anderson , Orit Rozenblatt-Rosen , Jonathan Chen , Karin Pelka , Matan Hofree
IPC分类号： C12Q1/6886
摘要： The present invention is generally directed to a colorectal (CRC) cell atlas that provides methods of predicting outcomes of cancer patients and therapeutic targets for treating patients in need thereof. The atlas may be used to predict a response to immunotherapy, in particular checkpoint blockade therapy and adoptive cell transfer. Disclosed herein are previously unidentified gene programs in tumors that can be used to predict response and provide for therapeutic targets that can be used to shift a tumor to a responsive phenotype.
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公开(公告)号：US11209440B2
公开(公告)日：2021-12-28
申请号：US15245748
申请日：2016-08-24
申请人： THE BROAD INSTITUTE, INC. , THE BRIGHAM AND WOMEN'S HOSPITAL, INC. , PRESIDENT AND FELLOWS OF HARVARD COLLEGE , MASSACHUSETTS INSTITUTE OF TECHNOLOGY
发明人： Vijay Kuchroo , Aviv Regev , Jellert Gaublomme , Youjin Lee , Alexander K. Shalek , Chao Wang , Nir Yosef , Hongkun Park
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：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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公开(公告)号：US12049643B2
公开(公告)日：2024-07-30
申请号：US16630887
申请日：2018-07-13
申请人： The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
发明人： Aviv Regev , Ana C. Anderson , Vijay K. Kuchroo , Sema Kurtulus , Asaf Madi
IPC分类号： C12N5/0787 , A61K35/17 , A61P35/00 , C07K14/705 , C12N5/0783 , G01N33/569 , G01N33/574
CPC分类号： C12N5/0638 , A61K35/17 , C07K14/70503 , G01N33/56972 , G01N33/57492
摘要： The subject matter disclosed herein is generally directed to novel CD8+ tumor infiltrating lymphocyte (TIL) subtypes associated with response to immunotherapy treatment. Specifically, the subtypes are associated with checkpoint blockade therapy. Moreover, the subject matter disclosed herein is generally directed to methods and compositions for use of the subtypes. Also, disclosed herein are gene signatures and markers associated with the subtypes and use of said signatures and markers. Further disclosed are therapeutic methods of using said gene signatures and immune cell subtypes. Further disclosed are pharmaceutical compositions comprising populations of CD8+ TILs enriched for a specific subtype.
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公开(公告)号：US11981922B2
公开(公告)日：2024-05-14
申请号：US17063604
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.
发明人： Meromit Singer , Aviv Regev , Orit Rozenblatt-Rosen , Davide Mangani , Ana Carrizosa Anderson , Vijay K. Kuchroo , Linglin Huang
IPC分类号： A61K35/17 , A61K39/395 , C07K16/18 , C07K16/22 , C07K16/28 , C07K16/38 , C07K16/40 , C12N5/0783 , C12Q1/6886 , A61K39/00
CPC分类号： C12N5/0638 , A61K35/17 , A61K39/39541 , A61K39/3955 , C07K16/18 , C07K16/22 , C07K16/2803 , C07K16/2818 , C07K16/2827 , C07K16/2863 , C07K16/2896 , C07K16/38 , C07K16/40 , C12Q1/6886 , A61K2039/507 , C07K2317/76 , C12Q2600/106
摘要： The present invention is generally directed to identify interacting cells in the tumor microenvironment and using the identified interactions to enhance anti-tumor immunity in cancer. Identified interactions can be modulated using therapeutic agents. Immune cells resistant to suppression can be used for adoptive cell transfer. The present invention is also generally directed to cell types and genes that are correlated to time of tumor growth and tumor size.
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公开(公告)号：US11884717B2
公开(公告)日：2024-01-30
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： A61K38/20 , A61K38/17 , C07K14/705 , A61P37/00 , A61P1/00 , A61P35/00 , A61K39/395 , A61K45/06 , C07K14/54 , C07K16/24 , C07K16/28 , C12N15/113 , A61K39/00
CPC分类号： C07K14/70596 , A61K38/177 , A61K38/1709 , A61K38/208 , A61K39/3955 , A61K45/06 , A61P1/00 , A61P35/00 , A61P37/00 , C07K14/5434 , C07K16/244 , C07K16/2896 , C12N15/1136 , C12N15/1138 , A61K2039/575 , C12N2310/11 , C12N2310/14 , C12N2310/20 , A61K38/208 , A61K38/1709
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：US11793787B2
公开(公告)日：2023-10-24
申请号：US17065328
申请日：2020-10-07
申请人： The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
IPC分类号： A61K31/4015 , C12N15/113 , C12N9/10 , C07K16/28 , A61K9/00
CPC分类号： A61K31/4015 , C12N9/10 , C12N15/113 , A61K9/0019 , C07K16/2818 , C07K16/2827 , C12N2310/20
摘要： The subject matter disclosed herein is generally directed to modulating anti-tumor T cell immunity by modulating steroidogenesis. Steroidogenesis may be modulated with inhibitors of enzymes that synthesize glucocorticoids in a tumor. The inhibitor may target Cyp11a1. The inhibitor may be metyrapone. The invention further relates to modulating immune states, such as CD8 T cell immune states, in vivo, ex vivo and in vitro. The invention further relates to diagnostic and screening methods.
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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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