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公开(公告)号：US20220023346A1
公开(公告)日：2022-01-27
申请号：US17381693
申请日：2021-07-21
发明人： Michael Thomas BETHUNE , Yi ZHANG , Thomas John VAN BLARCOM , Siler PANOWSKI , Barbra Johnson SASU
IPC分类号： A61K35/17 , C12N15/86 , C07K14/725 , C12N5/0783
摘要： Provided herein are recombinant antigen receptors, for example chimeric antigen receptors (CARs), that comprise modified cytoplasmic domains that provide improved signalling and thereby provide improved performance and safety. Also provided are polynucleotides encoding the recombinant antigen receptors, vectors comprising the polynucleotides, and engineered immune cells comprising the vectors and/or polynucleotides. The invention further provides methods for engineering immune cells to express the recombinant antigen receptors. Improved recombinant antigen receptor signalling is also provided by co-expressing a first recombinant antigen receptor and a second recombinant antigen receptor or co-expressing a recombinant antigen receptor and a protein involved in transducing the signal from the activated recombinant antigen receptor. Also provided are methods of treating a variety of conditions, including, but not limited to, blood cancers and cancers characterized by solid tumors, by administering the engineered cells to patients suffering from such a condition.
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公开(公告)号：US20200339944A1
公开(公告)日：2020-10-29
申请号：US16857394
申请日：2020-04-24
IPC分类号： C12N5/00 , C12N5/0783 , A61K35/17
摘要： Described herein are improved media for culturing immune cells, and methods of use thereof. In particular, cell growth media described herein are particularly suitable for T-cell expansion, which can be used for manufacture of cells useful in adoptive cell therapies, including therapies using chimeric antigen receptors (e.g., CAR-T cell therapy).
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公开(公告)号：US20200276238A1
公开(公告)日：2020-09-03
申请号：US16804545
申请日：2020-02-28
IPC分类号： A61K35/17 , C07K14/715 , C07K16/28 , C12N15/67 , C07K16/30
摘要： Provided herein are PD-1 chimeric cytokine receptors. When present on chimeric antigen receptor (CAR)-bearing immune cells, such receptors allow for increased immune cell activation, proliferation, persistence, and/or potency, when engaged with PD-1 ligands or activation with an anti-PD-1 antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.
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公开(公告)号：US20240016846A1
公开(公告)日：2024-01-18
申请号：US18365014
申请日：2023-08-03
IPC分类号： A61K35/17 , C07K14/715 , C07K16/28 , C07K16/30 , C12N15/67
CPC分类号： A61K35/17 , C07K14/7155 , C07K16/2818 , C07K16/30 , C12N15/67 , A61K38/00
摘要： Provided herein are PD-1 chimeric cytokine receptors. When present on chimeric antigen receptor (CAR)-bearing immune cells, such receptors allow for increased immune cell activation, proliferation, persistence, and/or potency, when engaged with PD-1 ligands or activation with an anti-PD-1 antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.
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5.发明公开公开(公告)号：US20230346934A1
公开(公告)日：2023-11-02
申请号：US18191955
申请日：2023-03-29
发明人： Yi ZHANG , Silvia K. TACHEVA-GRIGOROVA , Barbra Johnson SASU , Siler PANOWSKI , Regina Junhui LIN , Zhe LI
IPC分类号： A61K39/00 , C07K14/705 , C07K14/71 , C07K16/28 , C07K16/22 , C07K14/725 , A61P35/00
CPC分类号： A61K39/4611 , C07K14/70521 , C07K14/71 , C07K16/2827 , C07K16/22 , C07K14/70507 , C07K14/70517 , C07K14/7051 , A61K39/4631 , A61K39/4643 , A61P35/00 , C07K2319/03 , C07K2317/622 , C07K2319/02 , A61K2239/13 , A61K2239/21 , A61K2239/22 , A61K2239/23 , A61K2239/28
摘要： Provided herein are chimeric switch receptors (CSRs) comprising an ectodomain and/or transmembrane domain derived from an inhibitory receptor (e.g. PD1 or TGFβR2) fused to the transmembrane domain and/or intracellular signaling domain derived from one or more costimulatory proteins (e.g. CD2, CD28, MyD88, DAP10 or ICOS), or variants thereof. The chimeric switch receptors are designed to convert a signal e.g. an inhibitory signal such as an immunosuppressive signal in the form of PD-L1 or TGFβ into a costimulatory signal. Also provided are engineered immune cells engineered to functionally express a chimeric switch receptor and/or a CAR and optionally also a chimeric cytokine receptor (CCR), and populations thereof, methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating e.g. cancer (e.g. solid or hematologic tumors) by administering the cells and the compositions.
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公开(公告)号：US20210107979A1
公开(公告)日：2021-04-15
申请号：US16802822
申请日：2020-02-27
发明人： Yi ZHANG , Thomas John VAN BLARCOM , Siler PANOWSKI , Silvia K. TACHEVA-GRIGOROVA , Barbra Johnson SASU
摘要： Provided herein are DLL3 binding agents and chimeric antigen receptors (CARs) comprising a DLL3 binding molecule that specifically binds to DLL3; and immune cells comprising these DLL3-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using DLL3-specific CARs, and immune cells comprising DLL3-specific CARs.
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公开(公告)号：US20240360196A1
公开(公告)日：2024-10-31
申请号：US18607387
申请日：2024-03-15
发明人： Arvind RAJPAL , Shobha Chowdary POTLURI , Laurent POIROT , Alexandre JUILLERAT , Thomas Charles PERTEL , Donna Marie STONE , Barbra Johnson SASU
IPC分类号： C07K14/705 , A61K35/17 , A61K39/00 , C07K14/725 , C07K16/28 , C07K16/30 , C12N5/0783
CPC分类号： C07K14/70503 , A61K35/17 , C07K14/7051 , C07K14/70517 , C07K14/70521 , C07K14/70578 , C07K16/2803 , C07K16/3069 , C12N5/0636 , A61K2039/5156 , C07K2317/622 , C07K2317/76 , C07K2319/03 , C07K2319/70 , C07K2319/74 , C12N2510/00
摘要： The invention relates to an inhibitory chimeric antigen receptor (N-CAR) comprising
an extracellular domain comprising an antigen binding domain,
a transmembrane domain and,
an intracellular domain
wherein the intracellular domain comprises an Immunoreceptor Tyrosine-based Switch Motif ITSM, wherein said ITSM is a sequence of amino acid TX1YX2X3X4, wherein
X1 is an amino acid
X2 is an amino acid
X3 is an amino acid and
X4 is V or I.-
公开(公告)号：US20230287120A1
公开(公告)日：2023-09-14
申请号：US18308143
申请日：2023-04-27
发明人： Yi ZHANG , Thomas John VAN BLARCOM , Siler PANOWSKI , Silvia K. TACHEVA-GRIGOROVA , Barbra Johnson SASU
CPC分类号： C07K16/2809 , A61P35/00 , C07K16/2887 , C12N15/63 , A61K2039/505
摘要： Provided herein are DLL3 binding agents and chimeric antigen receptors (CARs) comprising a DLL3 binding molecule that specifically binds to DLL3; and immune cells comprising these DLL3-specific CARs, e.g., CAR-T cells. Also provided are methods of making and using DLL3-specific CARs, and immune cells comprising DLL3-specific CARs.
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9.发明申请公开(公告)号：US20220409665A1
公开(公告)日：2022-12-29
申请号：US17841041
申请日：2022-06-15
发明人： Elvin J. LAURON , Siler PANOWSKI , Barbra Johnson SASU , Cesar Adolfo SOMMER , Surabhi SRIVATSA SRINIVASAN , Thomas John VAN BLARCOM , Shanshan LANG
摘要： Provided herein are CD70-binding proteins comprising a CD70-binding domain and a transmembrane domain, engineered immune cells comprising the CD70-binding proteins, and methods of making and using the same. Also provided herein are engineered immune cells e.g. CAR (chimeric antigen receptor) T cells for administration to patients to treat cancer (e.g., solid tumors and hematologic tumors) and other unwanted conditions. The cells are engineered to functionally express a first antigen binding molecule e.g. a CD70 CAR and a second antigen binding molecule e.g. a second CAR that binds a target molecule characteristic of the cancer or other disease or unwanted condition. The cells may be further engineered to reduce the functional expression level of one or more of TRAC, CD52 and CD70. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering them.
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公开(公告)号：US20240042030A1
公开(公告)日：2024-02-08
申请号：US18361056
申请日：2023-07-28
IPC分类号： A61K39/00 , C12N15/113 , C12N5/0783 , A61P35/00
CPC分类号： A61K39/4631 , C12N15/113 , A61K39/4613 , C12N5/0646 , A61P35/00 , C12N2510/00
摘要： Provided herein are engineered immune cells and populations thereof for administration to subjects to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of CD48, CD58, ICAM-1, RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) and/or a CD70 binding protein to target tumor cells or other damaged cells in the subject and/or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.
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