公开(公告)号：US11331269B2

公开(公告)日：2022-05-17

申请号：US16449100

申请日：2019-06-21

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

发明人： Chengcheng Jin ,  Georgia Lagoudas ,  Paul Blainey ,  Tyler Jacks

IPC分类号： A61K45/00 ,  A61K9/00 ,  A61P35/00 ,  C07K16/24 ,  C07K16/28 ,  A61K31/43 ,  A61K31/7036 ,  A61K31/4164 ,  A61K38/08 ,  A61K31/7052 ,  A61K31/7048 ,  A61K31/7056 ,  A61K45/06

摘要： It has been discovered that lung tumor growth is associated with a dysregulation of the local microbiota, including an increased total bacterial load and reduced bacterial diversity in the airway. In the lungs, commensal bacteria, which are otherwise non-pathogenic and colonize pulmonary tissue at a much lower density in healthy individuals, provoke chronic inflammation and exacerbation of lung cancer through tumor-infiltrating immune cells. Thus, targeting the lung microbiota and its responding immune pathways is useful in treating lung cancer. Disclosed are compositions and methods targeting the lung microbiota and its responding immune pathways in a subject by specific targeting of commensal bacteria in the subject. Typically, the methods involve administering an effective amount of one or more therapeutics such as an antibiotic that reduces the local bacterial load, blocks or depletes tumor-infiltrating immune cells, and/or locally inhibits one or more cytokines or chemokines.

公开(公告)号：US20200216551A1

公开(公告)日：2020-07-09

申请号：US16735187

申请日：2020-01-06

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

发明人： Amy Li ,  Rebecca H. Herbst ,  Aviv Regev ,  Tyler Jacks ,  David Canner

IPC分类号： C07K16/28 ,  C07K16/24 ,  C07K16/30 ,  C12N9/22 ,  A61P35/00

摘要： The present invention discloses novel methods, compositions, and uses thereof for removing or overcoming immunosuppression. More specifically, the methods and compositions disclosed herein target effector Treg cells by modulating ST2 and/or IL-33 signaling using pharmaceutical inhibitors and/or genetic ablation, whereby the levels and/or activities of effector Treg cells in a tumor microenvironment are inhibited, and the infiltration of effector CD8+ cytotoxic T cells into tumor microenvironment increases. As a result, tumor growth is inhibited and tumor volume is reduced. The present invention also provides methods for identifying and isolating effector Treg cells in a population of heterogeneous cells.

公开(公告)号：US20240043934A1

公开(公告)日：2024-02-08

申请号：US18021625

申请日：2021-08-22

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

发明人： Aviv Regev ,  William Hwang ,  Karthik Jagadeesh ,  Jimmy Guo ,  Tyler Jacks ,  Hannah Hoffman

IPC分类号： C12Q1/6886

CPC分类号： C12Q1/6886 ,  C12Q2600/112 ,  G01N2800/7028

摘要： Described herein are pancreatic ductal adenocarcinoma (PDAC) signatures and methods of detecting the same in a sample from heterogeneity-score a subject. Also described herein, are methods of methods of diagnosing, prognosing, and/or treating PDAC in a subject that can include detecting one or more of the PDAC signatures.

公开(公告)号：US11739156B2

公开(公告)日：2023-08-29

申请号：US16735187

申请日：2020-01-06

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

发明人： Amy Li ,  Rebecca H. Herbst ,  Aviv Regev ,  Tyler Jacks ,  David Canner

IPC分类号： C07K16/28 ,  C07K16/24 ,  C07K16/30 ,  A61P35/00 ,  C12N9/22 ,  A61K39/00 ,  A61K45/06

CPC分类号： C07K16/2866 ,  A61P35/00 ,  C07K16/244 ,  C07K16/30 ,  C12N9/22 ,  A61K45/06 ,  A61K2039/505 ,  C07K2317/732

摘要： The present invention discloses novel methods, compositions, and uses thereof for removing or overcoming immunosuppression. More specifically, the methods and compositions disclosed herein target effector Treg cells by modulating ST2 and/or IL-33 signaling using pharmaceutical inhibitors and/or genetic ablation, whereby the levels and/or activities of effector Treg cells in a tumor microenvironment are inhibited, and the infiltration of effector CD8+ cytotoxic T cells into tumor microenvironment increases. As a result, tumor growth is inhibited and tumor volume is reduced. The present invention also provides methods for identifying and isolating effector Treg cells in a population of heterogeneous cells.

公开(公告)号：US20200078296A1

公开(公告)日：2020-03-12

申请号：US16449100

申请日：2019-06-21

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

发明人： Chengcheng Jin ,  Georgia Lagoudas ,  Paul Blainey ,  Tyler Jacks

IPC分类号： A61K9/00 ,  A61K45/06 ,  A61P35/00 ,  C07K16/24 ,  C07K16/28 ,  A61K31/43 ,  A61K31/7036 ,  A61K31/4164 ,  A61K38/08 ,  A61K31/7052 ,  A61K31/7048 ,  A61K31/7056

摘要： It has been discovered that lung tumor growth is associated with a dysregulation of the local microbiota, including an increased total bacterial load and reduced bacterial diversity in the airway. In the lungs, commensal bacteria, which are otherwise non-pathogenic and colonize pulmonary tissue at a much lower density in healthy individuals, provoke chronic inflammation and exacerbation of lung cancer through tumor-infiltrating immune cells. Thus, targeting the lung microbiota and its responding immune pathways is useful in treating lung cancer. Disclosed are compositions and methods targeting the lung microbiota and its responding immune pathways in a subject by specific targeting of commensal bacteria in the subject. Typically, the methods involve administering an effective amount of one or more therapeutics such as an antibiotic that reduces the local bacterial load, blocks or depletes tumor-infiltrating immune cells, and/or locally inhibits one or more cytokines or chemokines.