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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：US20230279351A1
公开(公告)日：2023-09-07
申请号：US17596493
申请日：2020-06-24
申请人： Seattle Children's Hospital (dba Seattle Children's Research Institute) , Benaroya Research Institute at Virginia Mason
发明人： Jane Buckner , David J. Rawlings , Karen Sommer , Yuchi Chiang Honaker , Peter Cook , Akhilesh Kumar Singh , Soo Jung Yang
IPC分类号： C12N5/0783 , C07K14/47 , C07K14/725
CPC分类号： C12N5/0637 , C07K14/4702 , C07K14/7051 , C12N2310/20 , C12N2510/00
摘要： Some embodiments of the compositions and methods disclosed herein include gene-edited, artificial immunoregulatory T cells (airT cells) comprising a constitutively expressed FoxP3 gene product expressed at a level equal to or greater than the level of FoxP3 expression in natural T regulatory (Treg or suppressor T) cells, and a transduced (e.g., artificially engineered by gene editing, viral vector transduction, transfection or other genetic engineering methodologies) T cell receptor (TCR). In some embodiments, the TCR is preferably specific for an antigen associated with an autoimmune, allergic, or other inflammatory condition. Some embodiments include methods for the preparation and/or use of airT cells. Some such embodiments include use of airT cells for the treatment and/or amelioration of a disorder, in which antigen-specific immunosuppression may be beneficial, such as an autoimmune, allergic, or other inflammatory disorder.
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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：US20220364176A1
公开(公告)日：2022-11-17
申请号：US17870886
申请日：2022-07-22
申请人： Washington State University , Seattle Children's Hospital DBA Seattle Children's Research Institute
IPC分类号： C12Q1/6883
摘要： Provided herein are epigenetic modifications that are associated with prior exposure to chemotherapy agents. In particular, differential DNA methylation regions (DMRs) that are characteristic of, and can thus be used to identify and/or treat, a male subject who has undergone chemotherapy are provided. The DMRs are used to screen for pregnancy complications, infertility, and passage of heritable mutations to an infant.
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公开(公告)号：US20220193136A1
公开(公告)日：2022-06-23
申请号：US17569107
申请日：2022-01-05
申请人： The Regents of the University of California , Seattle Children's Hospital DBA Seattle Children's Research Institute
发明人： Yvonne Y. CHEN , Eugenia ZAH , Michael C. JENSEN
IPC分类号： A61K35/17 , C07K16/46 , C12N5/0783 , C07K16/28 , C07K14/725 , C07K14/705
摘要： A CD19-OR-CD20 chimeric antigen receptor (CAR) protein construct is provided. Also provided are nucleic acids encoding the CD19-OR-CD20 CAR; and methods of use, e.g. in the treatment of B cell malignancies. The CD19-OR-CD20 CAR of the invention is a bispecific CAR that can trigger T-cell activation upon detection of either CD19 or CD20 (or both). It is a single molecule that confers two-input recognition capability upon human T cells engineered to stably express this CAR.
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公开(公告)号：US20220120745A1
公开(公告)日：2022-04-21
申请号：US17458958
申请日：2021-08-27
申请人： The University of Queensland , Seattle Children's Hospital dba Seattle Children's Research Institute
IPC分类号： G01N33/566 , G01N33/543 , G01N33/569
摘要： The present disclosure relates to biofragment compositions that comprise bioparticle fragments and at least one heterologous antigen-binding molecule. In some embodiments, the biofragment is typically derived from a larger, intact bioparticle that express the at least one heterologous antigen-binding molecule at the surface, and the biofragment has increased solubility to facilitate assays for antigen detection. The disclosure also relates the related methods of using and making the biofragment compositions, as well as systems and devices implementing the biofragment compositions. In some embodiments, the related methods, systems and devices do not require additional detection reagents, such as animal derived detection antibodies.
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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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