Abstract: Methods to promote thymic regeneration are described. The methods can inhibit nucleotide-binding oligomerization domain-containing protein 2 (NOD2), Rho GTPases, and/or microRNA 29c (miR29c). These inhibition methods can promote regenerative molecules, such as interleukin (IL)-22, IL-23, and/or bone morphogenetic protein 4 (BMP4). Promoting thymic regeneration can be beneficial in patients due to age, infection, or cancer therapies.
Abstract: The present disclosure relates to anti-ROR1 binding proteins, including those that bind to a ROR1 or portion thereof such as an intracellular C terminal portion of a ROR1 protein, and the use of such binding proteins in immunohistochemical and diagnostic methods. Related kits and methods of using the binding proteins are also provided, as are methods of treatment of subjects having diseases or conditions determined to be candidates for such treatments by the binding proteins or methods of this disclosure.
Type:
Grant
Filed:
February 2, 2017
Date of Patent:
April 6, 2021
Assignee:
FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Ashwini Balakrishnan, Benjamin G. Hoffstrom, Julie Randolph-Habecker, Stanley R. Riddell
Abstract: The present invention provides a method of carrying out adoptive immunotherapy in a primate subject in need thereof by administering the subject a cytotoxic T lymphocytes (CTL) preparation in a treatment-effective amount. The method comprises administering as the CTL preparation a preparation consisting essentially of an in vitro expanded primate CTL population, the CTL population enriched prior to expansion for central memory T lymphocytes, and depleted prior to expansion of effector memory T lymphocytes. In some embodiments, the method may further comprise concurrently administering Interleukin-15 to the subject in an amount effective to increase the proliferation of the central memory T cells in the subject. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.
Type:
Grant
Filed:
July 17, 2019
Date of Patent:
April 6, 2021
Assignees:
City of Hope, Fred Hutchinson Cancer Research Center
Inventors:
Stanley R. Riddell, Susanna Carolina Berger, Michael C. Jensen
Abstract: Small cell lung cancer specific chimeric antigen receptor comprising: an antigen-binding domain capable of specifically binding an antigen selected from Tables 1A, 1B, 2A, 2B and 4 and/or that specifically binds to or interacts GAD65, PTPRU, TFRC and GABA-b. A method for treating a subject suffering from SCLC comprising, introducing into the subject a therapeutically effective amount of a T lymphocyte comprising a chimeric antigen receptor. An antigen binding molecule, comprising: an antigen-binding domain capable of specifically binding an antigen selected from Tables 1A, 1B, 2A, 2B and 4 and/or that specifically binds to or interacts GAD65, PTPRU, TFRC and GABA-b. A method of detecting an SCLC tumor in a subject.
Type:
Application
Filed:
September 18, 2020
Publication date:
March 25, 2021
Applicant:
FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Paul Lampe, Ashley McGarry Houghton, Kristin Lastwika
Abstract: Methods to create chemically-induced dimerizing (CID) protein systems and uses thereof are described. The methods utilize antibody binding domain dimerizing proteins. The created systems can be used to regulate cellular events such as gene expression, receptor signaling and cell death to effectuate a variety of clinically relevant treatment outcomes.
Abstract: A platform for ex vivo isolation, production, and formulation of genetically-modified cells is described. The platform utilizes a software-enabled point-of-care and/or portable device making gene therapy more widely available.
Abstract: The present disclosure relates to anti-ROR1 binding proteins, including those that bind to a ROR1 or portion thereof such as an intracellular C terminal portion of a ROR1 protein, and the use of such binding proteins in immunohistochemical and diagnostic methods. Related kits and methods of using the binding proteins are also provided, as are methods of treatment of subjects having diseases or conditions determined to be candidates for such treatments by the binding proteins or methods of this disclosure.
Type:
Grant
Filed:
February 2, 2017
Date of Patent:
February 23, 2021
Assignee:
FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Ashwini Balakrishnan, Benjamin G. Hoffstrom, Julie Randolph-Habecker, Stanley R. Riddell
Abstract: The present disclosure provides compositions, kits, and methods to protect organs by inducing acquired cytoresistance without causing injury to the organ. The compositions, kits, and methods utilize heme proteins, iron and/or vitamin B12 and, optionally, agents that impact heme protein metabolism.
Abstract: The present disclosure provides compositions and methods for the delivery of immune cells to treat un-resectable or non-resected tumor cells and tumor relapse. The compositions comprise (i) a structure comprising an injectable polymer or scaffold comprising pores; (ii) lymphocytes disposed within the structure, (iii) at least one lymphocyte-adhesion moiety associated with the structure; and (iv) at least one lymphocyte-activating moiety associated with the structure, and optionally an immune stimulant.
Abstract: In one aspect, the present invention provides an intron-modified capsid expression cassette useful for generating adeno-associated virus (AAV) vector particles. In another aspect, the present invention provides a method of reducing the immune response in a mammalian subject undergoing treatment with an AAV vector.
Type:
Application
Filed:
July 30, 2020
Publication date:
January 14, 2021
Applicant:
Fred Hutchinson Cancer Research Center
Inventors:
Arthur Dusty Miller, Christine L. Halbert, Michael J. Metzger
Abstract: The present disclosure provides methods for generating enhanced affinity T cell receptors by agonist selection of hematopoietic progenitor cells expressing an antigen specific TCR? cultured with stromal cells expressing Delta-like-1 or Delta-like-4, compositions prepared from such methods, and uses of thereof.
Abstract: The present disclosure provides compositions and uses thereof for treating a disease or disorder associated with CD20 expression. Treatments of this disclosure include use of a host cell expressing a fusion protein, such as an anti-CD20 CAR, optionally in combination with a CD20-specific binding molecule, a chemotherapeutic, an inhibitor of an immunosuppression component, or combinations thereof.
Abstract: 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 embodiments 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. It has been surprisingly found that the length of the spacer region can affects the ability of chimeric receptor modified T cells to recognize target cells in vitro and affects in vivo efficacy of the chimeric receptor modified T cells. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.
Type:
Grant
Filed:
October 18, 2019
Date of Patent:
December 22, 2020
Assignees:
Fred Hutchinson Cancer Research Center, Seattle Children's Hospital
Inventors:
Michael C. Jensen, Stanley R. Riddell, Michael Hudecek
Abstract: Disclosed herein are to markers, methods and systems for identifying cell populations, diagnosing, monitoring and treating cancer, including biomarkers predictive of response to immunotherapy treatment in Merkel cell carcinoma.
Abstract: In one aspect, the invention provides a method of screening a human subject to determine if said subject has a genetic predisposition to develop, or is suffering from Facioscapulohumeral Dystrophy (FSHD), said method comprising: (a) providing a biological sample comprising genomic DNA from the subject; and (b) analyzing the portion of the genomic DNA in the sample corresponding to the distal D4Z4-pLAM region on chromosome 4 and determining the presence or absence of a polymorphism resulting in a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene, wherein a determination of the absence of a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene indicates that the subject does not have a genetic predisposition to develop, and is not suffering from FSHD, and/or wherein a determination of the presence of a functional polyadenylation sequence operationally linked to exon 3 of the DUX4 gene indicates that the subject has a genetic predisposition to devel
Type:
Grant
Filed:
August 18, 2011
Date of Patent:
December 15, 2020
Assignees:
Fred Hutchinson Cancer Research Center, University of Rochester, Leiden University Medical Center
Inventors:
Silvere M. van der Maarel, Stephen J. Tapscott, Rabi Tawil, Richard J. L. F. Lemmers, Linda Geng, Lauren Snider
Abstract: The present disclosure provides methods of using certain biomarker expression profiles in the detection, diagnosis, prognosis, or development of treatment regimens for various cellular hyperproliferative disorders of the bowel. For example, pre-diagnostic methods comprise detecting whether the concentration of at least BAG4 in a test biological sample from a subject is elevated as compared to a control.
Abstract: A platform for ex vivo isolation, production, and formulation of genetically-modified cells is described. The platform utilizes a software-enabled point-of-care and/or portable device making gene therapy more widely available.
Abstract: The present disclosure provides compositions and methods for boosting, augmenting or enhancing the efficacy of the adoptive cellular immunotherapy by using modified T cells expressing an antigen binding protein in conjunction with modified cells (such as hematopoietic progenitor cells, modified human immune system cells or a combination thereof) expressing the antigen specifically bound by the antigen binding protein of the modified T cells.
Type:
Grant
Filed:
October 27, 2015
Date of Patent:
November 10, 2020
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Susanna Carolina Berger, Stanley R. Riddell
Abstract: Chlorotoxin variants, chlorotoxin variant conjugates, compositions that include the chlorotoxin variants or conjugates, and methods for using the chlorotoxin variants, conjugates, and compositions.
Abstract: Single chain, multimerized, and/or glycosylated NKG2D decoys are described. The NKG2D decoys have high affinity and avidity for surface bound and soluble NKG2D ligands and can be used to (i) identify NKG2D ligands; (ii) treat cancer, graft vs. host disease (GVHD), and inflammatory conditions; and (iii) potentiate an immune response against a vaccine as well as many other potential uses.
Type:
Grant
Filed:
November 10, 2016
Date of Patent:
October 27, 2020
Assignee:
FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Mesfin Gewe, Roland K. Strong, Martin Prlic, Peter Rupert, Thomas Spies, Veronika Spies