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    EXPRESSION OF HUMAN FOXP3 IN GENE EDITED T CELLS
    33.
    发明申请
    EXPRESSION OF HUMAN FOXP3 IN GENE EDITED T CELLS 有权

    公开(公告)号：US20210253652A1

    公开(公告)日：2021-08-19

    申请号：US16981213

    申请日：2019-04-25

    申请人： Seattle Children's Hospital (dba Seattle Children's Research Institute)

    发明人： Andrew M. Scharenberg ,  David J. Rawlings ,  Karen Sommer ,  Yuchi Chiang Honaker ,  Iram F. Khan ,  Troy Torgerson

    IPC分类号： C07K14/47 ,  C12N15/86 ,  C12N15/90 ,  A61K35/17 ,  C12N5/0783 ,  A61P37/06

    摘要： Aspects of the invention described herein concern targeting of a FOXP3 cDNA, e.g., full-length human-codon optimized, into a FOXP3 locus or a non-FOXP3 locus so as to provide constitutive or regulated FOXP3 expression in a primary human lymphocyte. The compositions and materials described herein provide specificity for CRISPR/Cas-mediated gene regulation of murine, non-human primates or human FOXP3. Guide RNA sequences are used to target the FOXP3, AAVS1, and other candidate loci for CRISPR/Cas-mediated gene regulation, and gene delivery cassettes for HDR based gene-modification are provided. The alternative compositions described herein can be delivered in the form of Ribonucleoprotein (RNP) and may be used to target human and/or non-human primate FOXP3. Reagents are comprised of novel guide RNA sequences and can generate high frequency of on-target cleavage in combination with a Cas protein and novel gene delivery cassettes including FOXP3 cDNA+/−other cis linked gene products.

    CHIMERIC TRANSCRIPTION FACTOR VARIANTS WITH AUGMENTED SENSITIVITY TO DRUG LIGAND INDUCTION OF TRANSGENE EXPRESSION IN MAMMALIAN CELLS
    37.
    发明申请
    CHIMERIC TRANSCRIPTION FACTOR VARIANTS WITH AUGMENTED SENSITIVITY TO DRUG LIGAND INDUCTION OF TRANSGENE EXPRESSION IN MAMMALIAN CELLS 审中-公开

    公开(公告)号：US20200181624A1

    公开(公告)日：2020-06-11

    申请号：US16467015

    申请日：2017-12-11

    申请人： Seattle Children's Hospital (dba Seattle Children's Research Institute)

    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.

    EARLY INTERVENTION METHODS TO PREVENT OR AMELIORATE TOXICITY
    40.
    发明申请
    EARLY INTERVENTION METHODS TO PREVENT OR AMELIORATE TOXICITY 审中-公开

    公开(公告)号：US20190112379A1

    公开(公告)日：2019-04-18

    申请号：US16087488

    申请日：2017-03-22

    申请人： SEATTLE CHILDREN'S HOSPITAL (DBA SEATTLE CHILDREN'S RESEARCH INSTITUTE)

    发明人： Michael JENSEN ,  Rebecca GARDNER

    IPC分类号： C07K16/28 ,  A61K9/00 ,  A61P35/02

    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.