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公开(公告)号：US20240075064A1
公开(公告)日：2024-03-07
申请号：US18261761
申请日：2022-01-18
发明人： Kutlu Goksu Elpek , Celeste Richardson , Michelle Lois Fleury , James Alex Storer , Shyamsundar Subramanian , Mithun Khattar
IPC分类号： A61K35/17 , A61K39/00 , A61P35/00 , C07K14/54 , C12N5/0783
CPC分类号： A61K35/17 , A61K39/4611 , A61K39/46444 , A61P35/00 , C07K14/5443 , C12N5/0636
摘要： The present disclosure provides compositions and methods for expanding T cells or tumor infiltrating lymphocytes (TILs) in vitro. K562 feeder cells engineered to express a costimulatory molecule (e.g., 41BB ligand (41BBL)) and either interleukin 21 (IL21) or interleukin 7 (IL7) can be used in a rapid expansion protocol (REP) step to expand the T cells or TILs. Thus, provided herein is a culture comprising T-cells or TILs and modified K562 feeder cells. The T cells can be modified to express a chimeric antigen receptor (CAR) or a T cell receptor (TCR) or the TILs can be modified to express membrane-bound IL15 (mbIL15). The T cells or TILs can be expanded in vitro using aREP without the use of exogenous interleukin 2 (IL2), and the expanded cells can be used in adoptive cell therapy for treatment of cancer without concomitant use of an exogenous cytokine such as IL2.
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公开(公告)号：US11058725B2
公开(公告)日：2021-07-13
申请号：US17017670
申请日：2020-09-10
发明人： Kutlu Goksu Elpek , Dhruv Kam Sethi , Meghan C. Langley , Tucker Read Ezell , Dexue Sun , Jennifer Leah Gori , Geetha Hanna Mylvaganam , Michelle Ols , Michelle Fleury , Celeste Richardson , James A. Storer , Vipin Suri , Shyamsundar Subramanian , Colleen Foley , Molly Reed Perkins , Jeremy Hatem Tchaicha , Scott Francis Heller
IPC分类号： A61K35/17 , C12N15/86 , C07K14/54 , A61K31/433 , C12N9/88 , C12N15/867 , C12N15/864 , C12N15/869 , C12N15/861
摘要： The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.
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3.发明公开公开(公告)号：US20240131069A1
公开(公告)日：2024-04-25
申请号：US18501621
申请日：2023-11-02
发明人： Mithun Khattar , Shyamsundar Subramanian , Rachel Burga , Michelle Lynn Ols , Jan ter Meulen , Kyle Pedro , Jeremy Hatem Tchaicha
IPC分类号： A61K35/17 , A61P35/00 , C12N5/0783
CPC分类号： A61K35/17 , A61P35/00 , C12N5/0636
摘要： Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.
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公开(公告)号：US20240108722A1
公开(公告)日：2024-04-04
申请号：US18261765
申请日：2022-01-18
发明人： Kyle Pedro , James Alexander Storer , Jan ter Meulen , Rachel Burga , Mithun Khattar , Michelle Ols , Jeremy Tchaicha , Shyamsundar Subramanian
IPC分类号： A61K39/00 , A61P35/00 , C07K14/54 , C12N5/0783 , C12N15/86
CPC分类号： A61K39/4611 , A61K39/4632 , A61K39/4644 , A61P35/00 , C07K14/5443 , C12N5/0636 , C12N15/86 , A61K2039/5156 , C12N2501/2321 , C12N2501/599 , C12N2502/30 , C12N2510/00 , C12N2740/15043
摘要： Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using arapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.
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5.发明公开公开(公告)号：US20240226158A9
公开(公告)日：2024-07-11
申请号：US18501621
申请日：2023-11-03
发明人： Mithun Khattar , Shyamsundar Subramanian , Rachel Burga , Michelle Lynn Ols , Jan ter Meulen , Kyle Pedro , Jeremy Hatem Tchaicha
IPC分类号： A61K35/17 , A61P35/00 , C12N5/0783
CPC分类号： A61K35/17 , A61P35/00 , C12N5/0636
摘要： Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.
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6.发明申请公开(公告)号：US20220133801A1
公开(公告)日：2022-05-05
申请号：US17577940
申请日：2022-01-18
发明人： Mithun Khattar , Shyamsundar Subramanian , Rachel Burga , Michelle Lynn Ols , Jan ter Meulen , Kyle Pedro , Jeremy Hatem Tchaicha
IPC分类号： A61K35/17 , C12N5/0783 , A61P35/00
摘要： Provided herein are tumor-infiltrating lymphocytes (TILs) engineered to express a membrane-bound interleukin 15 (mbIL15). The mbIL15 TILs can be expanded in vitro using a rapid expansion protocol without the use of exogenous interleukin 2 (IL2) and can be used in adoptive cell therapy without concomitant use of an exogenous cytokine such as IL2. The TIL can be further engineered such that the mbIL15 is operably linked to one or more drug responsive domains (DRDs), polypeptides that can regulate the abundance and/or activity of the IL15 upon binding of the DRD with a ligand. Also provided herein are components for making the modified TILs and methods for making and using the modified TILs.
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