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公开(公告)号：US20230322937A1
公开(公告)日：2023-10-12
申请号：US18329987
申请日：2023-06-06
发明人： Michael C. Jensen , Rebecca Gardner
CPC分类号： C07K16/2866 , A61P35/02 , A61K2039/505 , A61K9/0053 , C07K2319/03 , A61K9/0019
摘要： Provided are methods for preventing or ameliorating toxicity caused by or due to a therapy, such as an immunotherapy or a cell therapy, by pre-emptive or early administration toxicity-targeting agent(s). In some embodiments, the therapy is a cell therapy in which the cells generally express recombinant receptors such as chimeric receptors, e.g., chimeric antigen receptors (CARs) or other transgenic receptors such as T cell receptors (TCRs). Features of the methods, including the timing of the administration of the agents or treatments for toxicity, provide various advantages, such as lower toxicity while maintaining persistence and efficacy of the administered cells.
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公开(公告)号：US20230303643A1
公开(公告)日：2023-09-28
申请号：US18021450
申请日：2021-08-18
IPC分类号： C07K14/47
CPC分类号： C07K14/4702 , C07K2319/00
摘要： Some embodiments of the methods and compositions provided herein relate to chimeric proteins comprising a T cell factor 1 (TCF1) domain and a β-catenin transactivation domain. In some embodiments, populations of cells containing such chimeric proteins have an increased level of memory T cell associated markers and activities compared to populations lacking the chimeric proteins. Some embodiments include populations of cells comprising the chimeric proteins and chimeric antigen receptors and uses thereof.
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公开(公告)号：US20230242936A1
公开(公告)日：2023-08-03
申请号：US17924811
申请日：2021-05-12
发明人： Michael C. Jensen , Jia Wei
CPC分类号： C12N15/85 , C12N15/635 , C12N5/0636 , C12N9/22 , C12N15/907 , A61K48/0066 , C12N2830/002 , C12N2830/20 , C12N2800/90
摘要： Some embodiments of the methods and compositions provided herein relate to systems comprising a promoter operably linked to a nucleic acid encoding a receptor, and an inducible promoter operably linked to a nucleic acid encoding a payload. In some embodiments, transcription from the inducible promoter is induced by activation of the receptor. In some embodiments, transcription from the inducible promoter is further modulated by inhibiting a signal between the activated receptor and the inducible promoter.
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公开(公告)号：US20230130938A1
公开(公告)日：2023-04-27
申请号：US17931258
申请日：2022-09-12
发明人： Michael C. Jensen
IPC分类号： A61K35/17 , A61P35/00 , C07K14/725 , C07K14/705 , C07K16/30 , C07K16/28
摘要： Disclosed herein are methods of engineering a bi-specific T-cell expressing chimeric antigen receptors for promoting the in vivo expansion and activation of an effector cell and a second chimeric antigen receptor or TcR specific for a ligand on a tumor. Methods of administering to subjects in need, bi-specific chimeric antigen receptor bearing cells are also provided.
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公开(公告)号：US20220380461A1
公开(公告)日：2022-12-01
申请号：US17812848
申请日：2022-07-15
发明人： Michael C. Jensen , Adam Johnson
IPC分类号： C07K16/28 , A61K35/28 , A61K38/17 , A61K39/395 , C07K14/725 , C07K14/705 , C07K14/71 , C07K14/715 , C07K16/32 , C12N5/0783 , C12N9/12 , C12N15/85 , A61K35/17
摘要： The present invention provides genetic tags operably linked to transgenes. The expression of the genetic tag allows identification, detection, selection, and ablation of cells expressing the transgene and the genetic tag. In some alternatives the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain and a polynucleotide coding for a genetic tag. In some alternatives the genetically modified host cell comprises a transgene comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain and a polynucleotide coding for a genetic tag, and wherein the polypeptide further comprises a flexible linker comprising amino acids GGGSGGGS (SEQ ID NO:45). Pharmaceutical formulations produced by the method, and methods of using the same, are also described.
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公开(公告)号：US20210371517A1
公开(公告)日：2021-12-02
申请号：US17097630
申请日：2020-11-13
发明人： Michael C. Jensen
IPC分类号： C07K16/28 , A61K35/17 , C12N5/0783 , C07K14/725 , C07K14/705 , C12N15/85 , A61K35/28 , A61K38/17 , C07K14/71 , C07K14/715 , C07K16/32 , A61K39/395 , C12N9/12
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 some alternatives 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. In some alternatives, the ligand binding domains binds to CD171.
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公开(公告)号：US20210324407A1
公开(公告)日：2021-10-21
申请号：US17271814
申请日：2019-08-28
发明人： Michael C. Jensen , Joshua Gustafson , Joseph Cheng , Rachel Wilson , Kamila Sabina Gwiazda , Jeremy Bjelajac
IPC分类号： C12N15/85
摘要： Some embodiments provided herein relate to gene delivery systems and methods using a single plasmid that carries a self-inactivating transposase gene and a corresponding transposon. Some embodiments include nucleic acids having certain sequences, vector including such nucleic acids, and compositions including the vectors.
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38.发明申请公开(公告)号：US20210139583A1
公开(公告)日：2021-05-13
申请号：US17096138
申请日：2020-11-12
发明人： Michael C. Jensen , Suzie Pun , Nataly Kacherovsky
IPC分类号： C07K16/28 , A61K35/17 , C12N5/0783 , C07K14/725 , C07K14/705 , C12N15/85 , A61K35/28 , A61K38/17 , C07K14/71 , C07K14/715 , C07K16/32 , A61K39/395 , C12N9/12
摘要： Aspects of the invention described herein include methods of treating, inhibiting, ameliorating and/or eliminating a virus or cancer cells in a subject utilizing genetically engineered human T-cells having receptors for a molecule presented by the virus or the cancer cells, wherein the genetically engineered T cells are isolated utilizing a two-stage MTX selection that employs increasing concentrations of MTX.
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公开(公告)号：US20210017246A1
公开(公告)日：2021-01-21
申请号：US16979475
申请日：2019-03-12
IPC分类号： C07K14/54 , C07K14/725
摘要： Some embodiments of the methods and compositions provided herein include cells having membrane-tethered, IL13 mutein-directed zetakine receptors, such as those which specifically bind to the IL-13 receptor alpha 2 (IL13Ra2) at a 50-fold higher affinity than wild-type IL-13, and methods of cell-based immunotherapy targeting cancer cells, such as cells of solid tumors, using these compositions. In some embodiments, the receptors include spacer regions, such as particular spacer regions designed to provide certain advantages.
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公开(公告)号：US20240043544A1
公开(公告)日：2024-02-08
申请号：US18265405
申请日：2021-12-03
发明人： Michael C. Jensen , Jia Wei
IPC分类号： C07K16/28
CPC分类号： C07K16/2863
摘要： Disclosed herein is a polynucleotide comprising a human codon-optimized sequence encoding a polypeptide comprising EGFR806CAR. The codon-optimized sequence may be incorporated into a construct comprising an optimal-functioning promoter, spacer, intracellular signaling domain, transmembrane domain, selection marker, at least one self-cleaving peptides, and EFGRt, in order to optimize expression. This sequence may then be expressed in cells, such as T cells, for the treatment or inhibition of a cancer, such as glioblastoma, liquid tumors, or solid tumors.
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