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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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2.发明授权公开(公告)号：US11957695B2
公开(公告)日：2024-04-16
申请号：US16396461
申请日：2019-04-26
申请人： The Broad Institute, Inc. , Massachusetts Institute of Technology , The Brigham and Women's Hospital, Inc.
IPC分类号： A61K31/573 , A61K35/17 , A61K38/20 , A61K45/06 , A61P35/00
CPC分类号： A61K31/573 , A61K35/17 , A61K38/20 , A61P35/00 , A61K45/06
摘要： The subject matter disclosed herein is generally directed to modulating T cell dysfunctional and effector states by modulating glucocorticoid and IL-27 signaling. 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：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：US20240108689A1
公开(公告)日：2024-04-04
申请号：US18273579
申请日：2022-01-21
申请人： The Brigham and Women's Hospital, Inc. , The Broad Institute, Inc. , The General Hospital Corporation , The Regents of the University of California
发明人： Vijay K. Kuchroo , Ramnik Xavier , Mathias Pawlak , David DeTomaso , Nir Yosef
IPC分类号： A61K38/17 , A61P37/02 , C12N5/0783 , C12N9/22
CPC分类号： A61K38/177 , A61P37/02 , C12N5/0636 , C12N9/22 , C12N2310/20 , C12N2501/2312 , C12N2501/2321 , C12N2501/2323 , C12N2503/02 , C12N2510/00
摘要： The subject matter disclosed herein is generally directed to pathogenic Th1 cells whose phenotype is dependent on IL-23R signaling. Th1 cell specific therapeutic targets and gene programs are disclosed herein. In particular, inhibition of CD160 reduces Th1 cell pathogenicity.
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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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