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    METHODS AND COMPOSITIONS FOR INDUCING NOTCH SIGNALING IN TUMOR MICROENVIRONMENTS
    1.
    发明申请
    METHODS AND COMPOSITIONS FOR INDUCING NOTCH SIGNALING IN TUMOR MICROENVIRONMENTS 有权

    公开(公告)号：US20220267437A1

    公开(公告)日：2022-08-25

    申请号：US17631399

    申请日：2020-07-28

    申请人： Fred Hutchinson Cancer Research Center

    发明人： Irwin D. Bernstein ,  Suzanne Furuyama

    IPC分类号： C07K16/28 ,  C07K14/705

    摘要： The disclosure provides methods for inducing Notch signaling in a targeted manner within aggregations of cells. The methods include contacting the aggregation of cells with a bi-specific molecule that facilitates trans-binding of Notch receptor. The bi-specific molecule comprising a cell-targeting domain that specifically binds to a cell-specific antigen expressed in the aggregation of cells, and a Notch-binding domain that specifically binds to Notch receptor. In some aspects, the disclosed methods and reagents provide methods of promoting pro-inflammatory states in tumor micro-environments.

    COMPOSITIONS AND METHODS FOR EXPANSION OF EMBRYONIC HEMATOPOIETIC STEM CELLS
    2.
    发明申请
    COMPOSITIONS AND METHODS FOR EXPANSION OF EMBRYONIC HEMATOPOIETIC STEM CELLS 审中-公开

    公开(公告)号：US20200046775A1

    公开(公告)日：2020-02-13

    申请号：US16656342

    申请日：2019-10-17

    申请人： Fred Hutchinson Cancer Research Center

    发明人： Irwin D. Bernstein ,  Brandon K. Hadland

    IPC分类号： A61K35/28 ,  C12N5/0789 ,  C07K14/52 ,  C12N5/0735

    摘要： The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types. The present invention also relates to administering the embryonic hematopoietic stem cells expanded using a combination of a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway to a patient for short-term and/or long-term in vivo repopulation benefits.

    Compositions and methods for expansion of embryonic hematopoietic stem cells
    5.
    发明授权
    Compositions and methods for expansion of embryonic hematopoietic stem cells 有权

    公开(公告)号：US10463698B2

    公开(公告)日：2019-11-05

    申请号：US15939199

    申请日：2018-03-28

    申请人： Fred Hutchinson Cancer Research Center

    发明人： Irwin D. Bernstein ,  Brandon K. Hadland

    IPC分类号： A61K35/28 ,  C12N5/073 ,  C12N5/0789 ,  C07K14/475 ,  C07K14/54 ,  C07K14/52 ,  C12N5/0735 ,  A61K35/12

    摘要： The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types. The present invention also relates to administering the embryonic hematopoietic stem cells expanded using a combination of a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGFβ pathway to a patient for short-term and/or long-term in vivo repopulation benefits.

    COMPOSITIONS AND METHODS FOR PROVIDING HEMATOPOIETIC FUNCTION WITHOUT HLA MATCHING
    6.
    发明申请
    COMPOSITIONS AND METHODS FOR PROVIDING HEMATOPOIETIC FUNCTION WITHOUT HLA MATCHING 审中-公开

    公开(公告)号：US20190298778A1

    公开(公告)日：2019-10-03

    申请号：US16378229

    申请日：2019-04-08

    申请人： Fred Hutchinson Cancer Research Center

    发明人： Irwin D. Bernstein ,  Colleen Delaney

    IPC分类号： A61K35/51 ,  C12N5/0789 ,  A61K35/50

    摘要： The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.

    COMPOSITIONS AND METHODS FOR PROVIDING HEMATOPOIETIC FUNCTION
    9.
    发明申请
    COMPOSITIONS AND METHODS FOR PROVIDING HEMATOPOIETIC FUNCTION 审中-公开

    公开(公告)号：US20200030384A1

    公开(公告)日：2020-01-30

    申请号：US16590255

    申请日：2019-10-01

    申请人： Fred Hutchinson Cancer Research Center

    发明人： Irwin D. Bernstein ,  Colleen Delaney

    IPC分类号： A61K35/51 ,  C12N5/0789 ,  A61K35/28 ,  A61K35/50 ,  G16B30/00

    摘要： The present invention relates to methods and compositions for providing hematopoietic function to human patients in need thereof, by selecting a pool of expanded human cord blood stem/progenitor cell samples for administration to the patient, wherein the samples in the pool collectively do not mismatch the patient at more than 2 of the HLA antigens or alleles typed in the patient; and administering the selected pool of expanded human cord blood stem/progenitor cell samples to the patient. Methods for obtaining the pools of expanded human cord blood stem/progenitor cell samples, banks of frozen pools of expanded human umbilical cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.