Abstract: This invention relates generally to compositions and methods for modulating complement component 3 (C3) activity or expression to treat, control or otherwise influence tumors and tissues, including cells and cell types of the tumors and tissues, and malignant, microenvironmental, or immunologic states of the tumor cells and tissues. The invention also relates to methods of diagnosing, prognosing and/or staging of tumors, tissues and cells.
Type:
Grant
Filed:
June 14, 2019
Date of Patent:
July 16, 2024
Assignees:
The Broad Institute, Inc., Massachusetts Institute of Technology, The Brigham and Women's Hospital, Inc.
Inventors:
Aviv Regev, Ana Carrizosa Anderson, Ayshwarya Subramanian, Orit Rozenblatt-Rosen
Abstract: This disclosure describes chimeric antigen receptors for expression in a Natural Killer (NK) cell, pharmaceutical compositions that include NK cells (and/or iPSCs) modified to express a chimeric antigen receptor, and methods involving such chimeric antigen receptors. Generally, the chimeric antigen receptor includes an ectodomain that includes an antigen recognition region, a transmembrane domain linked to the ectodomain, and an endodomain linked to the transmembrane domain. The endodomain can include a signaling peptide that activates an NK cell.
Type:
Grant
Filed:
April 1, 2020
Date of Patent:
July 9, 2024
Assignee:
Regents of the University of Minnesota
Inventors:
Dan Samuel Kaufman, David Lee Lampi Hermanson, Branden Scott Moriarity
Abstract: Claudin 18.2 T cell antigen couplers (TACs) polypeptides having (i) an antigen-binding domain that binds Claudin 18.2, (ii) an antigen-binding domain that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide are provided. Nucleic acids encoding the claudin 18/2 TACs are also provided.
Type:
Grant
Filed:
June 1, 2022
Date of Patent:
June 25, 2024
Assignee:
Triumvira Immunologics USA, Inc.
Inventors:
Andreas Bader, Christopher W. Helsen, Philbert Ip, Tania Benatar, Ling Wang
Abstract: The present invention discloses a recombinant bacteriophage comprising a phage genome polynucleotide including a gene encoding a heterologous antigen protein(s) and a killing gene encoding a protein that is capable of killing a host bacterium. Such a recombinant bacteriophage is designed to prime a subject's immune response and to kill the bacterium that it infects such that the “prime and kill” bacteriophage provides two lines of protection against infectious disease.
Abstract: Disclosed here is a generally applicable framework that utilizes massively-parallel single-cell RNA-seq to compare cell types/states found in vivo to those of in vitro models. Furthermore, Applicants leverage identified discrepancies to improve model fidelity. Applicants uncover fundamental gene expression differences in lineage-defining genes between in vivo systems and in vitro systems. Using this information, molecular interventions are identified for rationally improving the physiological fidelity of the in vitro system. Applicants demonstrated functional (antimicrobial activity, niche support) improvements in Paneth cell physiology using the methods.
Type:
Grant
Filed:
January 4, 2019
Date of Patent:
May 28, 2024
Assignees:
Massachusetts Institute of Technology, The Brigham and Women's Hospital, Inc.
Inventors:
Benjamin E. Mead, Jose Ordovas-Montanes, Alexander K. Shalek, Jeffrey Karp, Robert Langer
Abstract: Methods for the in vitro production of enucleated red blood cells and the enucleated red blood cells thus prepared are provided. Such enucleated red blood cells may express a sortaggable surface protein, which allows for surface modification in the presence of a sortase. Also described herein are surface modified enucleated red blood cells, e.g., conjugated with an agent of interest such as a peptide, a detectable label, or a chemotherapeutic agent, and uses thereof in delivering the agent to a subject.
Type:
Grant
Filed:
September 16, 2019
Date of Patent:
May 28, 2024
Assignee:
Whitehead Institute for Biomedical Research
Abstract: Disclosed herein are methods for producing genetically modified cells expressing HLA-G (e.g., cell surface HLA-G) persistently, and nucleic acid compositions useful for generating such genetically modified cells. Also disclosed are cell therapy methods that utilize genetically modified cells that express HLA-G persistently. The HLA-G genetic modifications described herein provide the cells with characteristics of reduced immunogenicity and/or improved immunosuppression, such that these cells have the promise of being universal or improved donor cells for transplants, cellular and tissue regeneration or reconstruction, and other therapies.
Abstract: A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.
Type:
Grant
Filed:
March 20, 2020
Date of Patent:
May 7, 2024
Assignee:
McMaster University
Inventors:
Jonathan Lorne Bramson, Christopher W. Helsen, Joanne Alicia Hammill, Kenneth Anthony Mwawasi
Abstract: Genetically modified mice characterized by one or more symptoms or signs associated with expression of human APOE4p and mouse Trem2p and relevant to non-familial late-onset Alzheimer's disease are provided wherein the genome of the mouse includes: 1) a DNA sequence encoding a human APOE4 protein (APOE4p) operably linked to a promoter; and 2) a DNA sequence encoding a mouse Trem2 protein having a mutation p,R47H (Trem2p) operably linked to a promoter, such that the mouse expresses human APOE4p and mouse Trem2p. Methods ace provided for screening for a compound for use in the treatment of Alzheimer's disease using such genetically modified mice.
Type:
Grant
Filed:
March 21, 2018
Date of Patent:
April 16, 2024
Assignees:
The Jackson Laboratory, Indiana University Research and Technology Corporation
Inventors:
Gareth Howell, Michael Sasner, Gregory Carter, Bruce Lamb
Abstract: The present invention provides compositions comprising an anti-CD7 chimeric activating receptor (CAR) and an anti-CD7 protein expression blocker, and methods of using such compositions in cancer therapy.
Type:
Grant
Filed:
July 14, 2022
Date of Patent:
April 2, 2024
Assignee:
NATIONAL UNIVERSITY OF SINGAPORE
Inventors:
Yi Tian Png, Natasha Vinanica, Takahiro Kamiya, Dario Campana
Abstract: Embodiments of the disclosure concern methods of identifying whether or not antigens from a particular pathogen are immunogenic, including the order of their immunogenicity. Other embodiments concern correlations between attributes of T cells and their clinical efficacy, such as mathematical representations thereof.
Type:
Grant
Filed:
September 21, 2021
Date of Patent:
March 19, 2024
Assignee:
Baylor College of Medicine
Inventors:
Ann Marie Leen, Pailbel Aguayo-Hiraldo, Ifigeneia Tzannou, Juan F. Vera Valdes
Abstract: Disclosed herein are cell preparations useful for modulating various peripheral immune functions, methods for making said cell preparations, and methods for their use.
Abstract: Provided are methods of treatment involving immunotherapy, such as T cell therapy, and administration of a tryptophan metabolism and/or kynurenine pathway modulator. In some embodiments, the method includes a combination therapy that involves administration of engineered T cells, such as chimeric antigen receptor (CAR)-expressing cells, and a tryptophan metabolism and/or kynurenine pathway modulator, such as an inhibitor of an enzyme. Also provided are engineered cells in which the expression of a molecule involved in the kynurenine pathway is modified. Also provided are methods of manufacturing engineered cells, cells, compositions, methods of administration to subjects, nucleic acids and kits for use in the methods. In some aspects, features of the methods and cells provide for increased or improved activity, activity, outcome, function, response, persistence, expansion and/or proliferation of cells for adoptive cell therapy.
Type:
Grant
Filed:
October 13, 2017
Date of Patent:
February 13, 2024
Assignee:
Juno Therapeutics, Inc.
Inventors:
Michael Ports, Evan Paul Thomas, Hyam I. Levitsky
Abstract: The invention includes compositions comprising at least one chimeric autoantibody receptor (CAAR) specific for an anti-phospholipase A2 receptor (PLA2R) autoantibody-based B cell receptor, polynucleotides encoding the CAAR, vectors comprising a polynucleotide encoding the CAAR, and recombinant T cells comprising the CAAR. The invention also includes methods of making a genetically modified cell, e.g., a genetically modified T cell, expressing a PLA2R-CAAR wherein the expressed CAAR comprises a PLA2R extracellular domain.
Type:
Grant
Filed:
December 6, 2021
Date of Patent:
January 30, 2024
Assignee:
The Trustees of the University of Pennsylvania
Inventors:
Saar Gill, Jonathan Hogan, Aimee S. Payne, Baomei Wang
Abstract: The present disclosure provides chimeric antigen receptors (CARs), particularly CARs that have adaptable receptor specificity (arCARs). Also provided are polypeptides of the CARs and other related molecules, polynucleotides, vectors, and cell compositions comprising the same. Pharmaceutical compositions comprising the polypeptides, polynucleotides, vectors, or cells of the present disclosure, and their uses in treating a disease in a subject are also provided.
Type:
Grant
Filed:
December 17, 2021
Date of Patent:
January 30, 2024
Assignee:
CENTURY THERAPEUTICS, INC.
Inventors:
Jill Marinari Carton, Michael Francis Naso, Luis Ghira Borges, John Wheeler, Andrew Devaney
Abstract: A trifunctional molecule is provided, comprising (i) a target-specific ligand, (ii) a ligand that binds a protein associated with a TCR complex, and (iii) a T cell receptor signaling domain polypeptide. Variants of the molecule are provided, including variants that exhibit optimized surface expression, transduction efficiency, and effector functionality. Variations include, for example, different ligands that bind CD3 epsilon (e.g., OKT3, L2K, F6A, UCHT1 and humanized UCHT1), different signaling domains, and different linkers between domains.
Type:
Grant
Filed:
March 22, 2023
Date of Patent:
January 23, 2024
Assignees:
Triumvira Immunologics USA, Inc., McMaster University
Inventors:
Jonathan Lorne Bramson, Christopher W. Helsen, Joanne Alicia Hammill, Kenneth Anthony Mwawasi
Abstract: Provided herein are T-cell receptor (TCR) fusion proteins (TFPs) having specificity for one or more tumor cell associated antigens, T cells engineered to express one or more TFP, and methods of use thereof for the treatment of diseases, including cancer.
Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.
Type:
Grant
Filed:
December 16, 2021
Date of Patent:
December 26, 2023
Assignee:
Hera Testing Laboratories, Inc.
Inventors:
Eric M. Ostertag, John Stuart Crawford, Joseph Ruiz