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1.发明公开公开(公告)号：US20230190796A1
公开(公告)日：2023-06-22
申请号：US16500352
申请日：2018-04-07
IPC分类号： A61K35/17 , C12N15/86 , C12N5/0783 , G01N33/569 , C07K14/725 , C07K14/47 , A61P35/00
CPC分类号： A61K35/17 , C12N15/86 , C12N5/0636 , G01N33/56972 , C07K14/7051 , C07K14/4748 , A61P35/00 , C12N2740/15043 , A61K38/00
摘要： Provided are cells, such as engineered cells, that express a prostate-specific membrane antigen (PSMA) or a modified form thereof. In some embodiments, the cell further contains a genetically engineered recombinant receptor, such as a chimeric antigen receptor, that specifically binds to an antigen. The present disclosure also provides methods of detecting, identifying, selecting or targeting cells expressing PSMA, such as in connection with administration of such cells to subjects, including methods of adoptive cell therapy, or in connection with methods of manufacturing engineered cells.
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公开(公告)号：US20190201442A1
公开(公告)日：2019-07-04
申请号：US15744744
申请日：2016-07-15
IPC分类号： A61K35/17 , C12N5/0783 , C12N15/86
摘要： Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells. In some embodiments, the antigen recognized by the engineered antigen receptor is related to a tumor antigen recognized by the engineered antigen receptor.
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3.发明申请公开(公告)号：US20200054673A1
公开(公告)日：2020-02-20
申请号：US16340085
申请日：2017-10-13
IPC分类号： A61K35/17 , A61K31/4245 , C07K14/725 , C12N5/0783 , C12N15/90 , G01N33/574
摘要： Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.
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公开(公告)号：US20220225597A1
公开(公告)日：2022-07-21
申请号：US16624766
申请日：2018-06-29
发明人： Eric Martin CHADWICK , Ronald James HAUSE, JR. , Yue JIANG , Hyam I. LEVITSKY , Ruth Amanda SALMON , Rafael Angel PONCE , Neis Eric OLSON
IPC分类号： A01K67/027 , G01N33/50 , A61K31/675 , A61K35/17 , A61K49/00 , C07K16/28 , C07K14/705 , C07K14/725
摘要： Provided herein is a model, in particular a mouse model, for assessing or evaluating toxicity to an immunotherapy, for example a therapeutic cell therapy, such as a cell therapy containing engineered cells, such as T cells, expressing a recombinant receptor, e.g. a chimeric antigen receptor (CAR). Also provided is a method for generating the mouse model. Also provided herein are methods of use for the mouse models of toxicity, such as to evaluate modified or alternative immunotherapies, and/or to evaluate test agents, including agents to assess as potential interventions to reduce, prevent, or ameliorate toxicity to immunotherapy in human subjects and/or for use in combination with an immunotherapy, e.g. CAR−T cell therapy.
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公开(公告)号：US20190292246A1
公开(公告)日：2019-09-26
申请号：US16345214
申请日：2017-11-03
发明人： Hyam I. LEVITSKY
IPC分类号： C07K16/18 , A61K31/444 , A61K31/675 , A61K9/00 , A61K35/17
摘要： Provided are methods, kits and compositions for ameliorating toxicity, such as cytokine release syndrome or neurotoxicity, suspected or being induced by or associated with, administration of a therapeutic agent, such as a immunotherapeutic agent targeting T cells and/or genetically engineered T cells, e.g. chimeric antigen receptor (CAR)-expressing T cells. The methods involve administering an additional agent, such as an agent having anti-oxidant or anti-inflammatory properties, that modulates immune cells such as by preventing or reducing the production of pro-inflammatory cytokines or stress cytokines and/or promoting differentiation to a neuroprotective phenotype, and/or capable of preventing, blocking or reducing microglial cell activation or function and/or capable of modulating, such as promoting, the activity of NRF2 or a component of an NRF2-regulated pathway, and/or one or more components involved in an antioxidant response element (ARE). The provided methods can be used in connection with or for methods of treating a disease or condition.
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公开(公告)号：US20200318070A1
公开(公告)日：2020-10-08
申请号：US16909928
申请日：2020-06-23
IPC分类号： C12N5/0783 , C07K16/30 , A61K39/00 , C07K14/725 , C07K14/705 , C07K16/40
摘要： Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some aspects, features of the cells and methods provide specificity and/or efficacy. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells.
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7.发明申请公开(公告)号：US20200292526A1
公开(公告)日：2020-09-17
申请号：US16644486
申请日：2018-09-07
IPC分类号： G01N33/50
摘要： Provided herein are methods for tracking certain cells associated with a cell therapy, such as from a starting cell composition or a sample prior to administration to a subject and from a sample following administration to a subject. In some aspects, the methods include assessing one or more parameters or attributes of such cells and methods of identifying cellular attributes associated with particular desired cells. The provided methods can be used in connection with cell therapy including adoptive transfer of engineered T cells or T cell precursors.
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公开(公告)号：US20190321403A1
公开(公告)日：2019-10-24
申请号：US16465109
申请日：2017-11-30
发明人： Hyam I. LEVITSKY
摘要： Provided herein are engineered B cells, such as for adoptive cell therapy. In some aspects, also provided are methods and compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some embodiments, the cells are engineered to produce and/or secrete an exogenous protein, such as a therapeutic protein, including antibodies and antigen-binding fragments thereof. In some aspects, features of the cells and methods provide for increased or improved activity, efficacy and/or persistence of the cells.
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公开(公告)号：US20170204372A1
公开(公告)日：2017-07-20
申请号：US15326441
申请日：2015-07-15
IPC分类号： C12N5/0783 , C07K14/705 , C07K16/40 , A61K39/00 , C07K14/725
摘要： Provided are engineered cells for adoptive therapy, including NK cells and T cells. Also provided are compositions for engineering and producing the cells, compositions containing the cells, and methods for their administration to subjects. In some aspects, features of the cells and methods provide specificity and/or efficacy. In some embodiments, the cells contain genetically engineered antigen receptors that specifically bind to antigens, such as chimeric antigen receptors (CARs) and costimulatory receptors. In some embodiments, the cells include receptors targeting multiple antigens. In some embodiments, the cells include repression of one or more gene product, for example, by disruption of a gene encoding the gene product. In some embodiments, a gene encoding an antigen recognized by the engineered antigen receptor is disrupted, reducing the likelihood of targeting of the engineered cells.
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