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公开(公告)号：US20220195441A1
公开(公告)日：2022-06-23
申请号：US17594542
申请日：2020-04-21
申请人： Seattle Children's Hospital (dba Seattle Children's Research Institute) , Fred Hutchinson Cancer Research Center
IPC分类号： C12N15/62 , C07K16/28 , C07K14/705 , C07K14/725 , C07K14/71
摘要： Some embodiments of the methods and compositions provided herein include chimeric antigen receptors (CAR)s which specifically bind to an epitope of CD33, such as an epitope encoded by exon 2 of CD33. Some embodiments include the use of such CARs for effective and safe therapies for myeloid leukemias, such as acute myeloid leukemia and chronic myeloid leukemia.
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公开(公告)号：US20180200298A1
公开(公告)日：2018-07-19
申请号：US15817002
申请日：2017-11-17
申请人： Fred Hutchinson Cancer Research Center , Seattle Children's Hospital, dba Seattle Children's Research Institute
IPC分类号： A61K35/17 , C07K16/40 , C07K14/705 , C07K16/32 , C07K16/28 , C07K14/715 , C07K14/725
摘要： The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.
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公开(公告)号：US20200078405A1
公开(公告)日：2020-03-12
申请号：US16657666
申请日：2019-10-18
申请人： Fred Hutchinson Cancer Research Center , Seattle Children's Hospital, dba Seattle Children's Research Institute
IPC分类号： A61K35/17 , C07K16/40 , C07K16/32 , C07K16/28 , C07K14/715 , C07K14/705 , C07K14/725
摘要： The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.
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公开(公告)号：US20210052649A1
公开(公告)日：2021-02-25
申请号：US17015995
申请日：2020-09-09
申请人： Fred Hutchinson Cancer Research Center , Seattle Children's Hospital, dba Seattle Children's Research Institute
IPC分类号： A61K35/17 , C07K14/705 , C07K14/725 , C07K14/715 , C07K16/28 , C07K16/32 , C07K16/40
摘要： The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and/or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor. In embodiments the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a ligand binding domain, a polynucleotide comprising a customized spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.
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公开(公告)号：US20230374104A1
公开(公告)日：2023-11-23
申请号：US18030476
申请日：2021-10-07
发明人： Michael C. Jensen , Adam Johnson , James Rosser
IPC分类号： C07K14/705 , C07K14/725
CPC分类号： C07K14/70596 , C07K14/7051
摘要： Some embodiments of the methods and compositions provided herein relate to chimeric proteins comprising a programmed cell death protein 1 (PD 1) extracellular domain and an intracellular immunostimulatory domain. Some embodiments include a cell containing a PD 1 chimeric polypeptide and a chimeric antigen receptor (CAR). In some embodiments, the CAR comprises a ligand binding domain capable of specifically binding to a target antigen on a solid tumor. More embodiments relate to therapies to treat, inhibit or ameliorate certain disorders, such as a cancer, such as a solid tumor.
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公开(公告)号：US20230068879A1
公开(公告)日：2023-03-02
申请号：US17758959
申请日：2021-02-02
IPC分类号： C07K14/725
摘要： Embodiments provided herein include methods and compositions comprising anti-dinitrophenol chimeric antigen receptors (CARs). Some embodiments include nucleic acids encoding such CARs, polypeptides encoded by such nucleic acids, cells comprising such nucleic acids or polypeptides, and methods utilizing such cells. Some embodiments also include the use of dinitrophenol (DNP) and derivatives thereof.
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公开(公告)号：US20210317407A1
公开(公告)日：2021-10-14
申请号：US17265484
申请日：2019-08-02
IPC分类号： C12N5/0783 , A61K35/17 , C07K16/44 , C07K14/73 , C07K14/705 , C07K16/28
摘要： Some embodiments of the methods and compositions provided herein relate to the use of hapten labeled cells to stimulate chimeric antigen receptor (CAR) T cells. In some embodiments, CAR T cells can include a CAR that specifically binds to a hapten. Some embodiments relate to the in vivo or in vitro stimulation CAR T cells by hapten labeled cells.
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公开(公告)号：US20200377911A1
公开(公告)日：2020-12-03
申请号：US16740995
申请日：2020-01-13
发明人： Andrew M. Scharenberg , David J. Rawlings , Michael C. Jensen , Kamila Sabina Gwiazda , Alexandra E. Grier
IPC分类号： C12N15/90 , C12N15/86 , A61K38/46 , A61P35/00 , A61K48/00 , C12N7/04 , C12N15/113 , C12N15/861
摘要： Disclosed herein are nuclease-based systems for genome editing and methods of using the system for genome editing. Also, disclosed are approaches to enhance Cas9-mediated gene editing efficiency in primary human cells with minimal toxicity when using adeno-associated virus vectors (AAV) to express the guide RNAs necessary for CRISPR/Cas9-based genome editing in the presence of helper proteins.
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公开(公告)号：US20200181624A1
公开(公告)日：2020-06-11
申请号：US16467015
申请日：2017-12-11
发明人： Michael C. Jensen , Tracy Ooi , Jia Wei
IPC分类号： C12N15/62 , C07K16/30 , C12N15/113
摘要： Provided herein is a system for inducible expression of a chimeric antigen receptor in cells, such as mammalian cells. The system comprises: a) a first nucleic acid comprising a first promoter inducible by a drug, wherein the first nucleic acid is operably linked to a first polynucleotide that encodes a chimeric antigen receptor, which comprises a ligand binding domain that is specific for a ligand selected from the group consisting of a tumor specific molecule, a viral specific molecule, and any other selected molecule expressed on a target cell population, wherein the ligand elicits recognition, modulation, inhibition, and/or elimination by a lymphocyte, a second polynucleotide, which encodes a spacer or an optimized polypeptide spacer, a third polynucleotide, which encodes a transmembrane domain and a fourth polynucleotide, which encodes an intracellular signaling domain and b) a second nucleic acid comprising a second promoter that is operably linked to a nucleic acid encoding a transcriptional activator for the first promoter inducible by drug, wherein the system is inducible by an amount of the drug that is less than a comparable system utilizing a wild type HEA3 chimeric transcription factor, or the system has an enhanced transcriptional expression at a given concentration of the drug compared to a wild type HEA3. Methods of making such cells and methods of treatment using these cells are also provided.
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公开(公告)号：US20200155597A1
公开(公告)日：2020-05-21
申请号：US16694024
申请日：2019-11-25
IPC分类号： A61K35/15 , C12N9/22 , C12N5/0786 , C07K14/705 , C07K14/56 , C07K14/52 , C07K14/47 , A61K35/17
摘要： Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and/or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.
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