Abstract: The current disclosure describes methods of expanding precursor cells for hematopoietic transplantation in subjects. The methods culture precursor cells in media containing an immobilized high molecular weight LILRB2 agonist or an LILRB2 agonist in combination with a Notch agonist. The expanded cells can be used to treat a variety of hematopoietic disorders.
Type:
Application
Filed:
June 26, 2019
Publication date:
October 31, 2019
Applicants:
Fred Hutchinson Cancer Research Center, Board of Regents of the University of Texas System
Inventors:
Irwin D. Bernstein, Chengcheng Zhang, Mi Deng, Zhigang Lu, Junke Zheng
Abstract: The present disclosure provides compositions and methods that rapidly and selectively modify cells of the immune system to achieve therapeutic objectives. The methods can be practiced in vivo and any cell type that expresses a known marker can be targeted for a therapeutic objective.
Abstract: Engineered and multimerized human immunodeficiency virus (HIV) envelope glycoproteins are described. The envelope glycoproteins can be multimerized using a heptamerization domain such as a C4b binding protein multimerization domain or a ferritin fusion. The engineered and multimerized envelope glycoproteins can derived from glycoprotein 120 (gp120) and can used as an HIV vaccine.
Type:
Application
Filed:
June 3, 2019
Publication date:
October 24, 2019
Applicant:
Fred Hutchinson Cancer Research Center
Inventors:
Roland K. Strong, Colin Correnti, Leonidas Stamatatos, Andrew McGuire
Abstract: The present disclosure provides compositions and methods for accurately detecting mutations by uniquely tagging double stranded nucleic acid molecules with dual cyphers such that sequence data obtained from a sense strand can be linked to sequence data obtained from an anti-sense strand when sequenced, for example, by massively parallel sequencing methods.
Abstract: The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.
Abstract: The present invention relates to methods and compositions for providing hematopoietic function in immunodeficient human patients, by selecting an expanded human umbilical cord blood stem/progenitor cell sample without taking into account the HLA-type of the expanded human cord blood stem/progenitor sample or the HLA-type of the patient; and administering the selected expanded human cord blood stem/progenitor cell sample to the patient. Methods for obtaining the expanded human cord blood stem/progenitor cell samples, banks of frozen expanded human cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.
Abstract: In one aspect, the present invention provides an intron-modified cap 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:
Grant
Filed:
November 10, 2011
Date of Patent:
September 17, 2019
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Arthur Dusty Miller, Christine L. Halbert, Michael J. Metzger
Abstract: Provided are methods, kits and compositions related to toxicity associated with administration of cell therapy for the treatment of diseases or conditions, e.g., cancer, including methods for use in predicting and treating a toxicity. In some embodiments, the toxicity is a neurotoxicity or cytokine release syndrome (CRS), such as a severe neurotoxicity or a severe CRS. The methods generally involve detecting a parameter of a biomarker or individually a parameter of each biomarker in a panel of biomarkers, such as a concentration, amount or activity, and comparing the detected parameter to a reference value for the parameter to determine if the subject is at risk for developing the toxicity, such as neurotoxicity or CRS or severe neurotoxicity or severe CRS.
Type:
Application
Filed:
December 2, 2016
Publication date:
September 12, 2019
Applicants:
Juno Therapeutics, Inc., Fred Hutchinson Cancer Research Center
Inventors:
He LI, Mark J. GILBERT, David MALONEY, Stanley R. RIDDELL, Cameron J. TURTLE
Abstract: Disclosed herein are compounds, and pharmaceutical compositions that include such compounds, for preventing or treating hearing loss. The compounds and pharmaceutical compositions described herein prevent or treat hair cell death. In addition, the compounds and pharmaceutical compositions described herein protect against kidney damage in an individual receiving an aminoglycoside antibiotic. Methods of using the compounds, alone or in combination with other therapeutic agents, are also disclosed.
Type:
Grant
Filed:
February 5, 2016
Date of Patent:
September 3, 2019
Assignees:
University of Washington, Oricula Therapeutics LLC, Fred Hutchinson Cancer Research Center
Inventors:
Julian Simon, Graham Johnson, Edwin W. Rubel, David W. Raible, Mario D. Gonzalez, Peter C. Meltzer, Weishi Miao
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:
June 12, 2014
Date of Patent:
September 3, 2019
Assignees:
City of Home, Fred Hutchinson Cancer Research Center
Inventors:
Stanley R. Riddell, Susanna Carolina Berger, Michael C. Jensen
Abstract: The invention is directed to methods for highly-multiplexed simultaneous detection of nucleic acids encoding paired adaptive immune heterodimers from a large number of biological samples containing lymphocytes of interest. Methods of the invention comprise performing a single pairing assay on a pool of source samples to determine nucleic acids encoding paired cognate receptor heterodimer chains in the combined pool. Separately, single-locus, high-throughput sequencing is performed on each individual sample to determine the plurality of sequences encoding one of the two receptor polypeptide chains. Pairs of cognate sequences determined in the pooled sample may then be mapped back to a single source sample by comparing the expression patterns of the single-locus sequences.
Type:
Grant
Filed:
October 29, 2015
Date of Patent:
August 27, 2019
Assignees:
ADAPTIVE BIOTECHNOLOGIES CORP., FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Ryan O. Emerson, Anna M. Sherwood, Harlan S. Robins
Abstract: The present disclosure provides compositions and methods that rapidly and selectively modify cells of the immune system to achieve therapeutic objectives. The methods can be practiced in vivo and any cell type that expresses a known marker can be targeted for a therapeutic objective.
Abstract: Systems and methods for detecting disseminated or circulating cells or DNA are described. The systems and methods utilize genetic constructs including unique genetic sequences. The genetic constructs can be used to tag and track cancer cells. Digital polymerase chain reaction (dPCR), among other methods, can be used to quantitatively track the cells following administration.
Abstract: This disclosure provides compositions and related methods providing targeted cell-specific inhibition of Notch receptor signaling. The disclosure provides a bi-specific molecule with separate domains that target the intended cell-type and the Notch receptor on that cell-type. The disclosure also provides for nucleic acids, vectors, and cells allowing for the expression of the bi-specific fusion molecules. The disclosure also provides related methods of making and using the bi-specific fusion molecule to inhibit Notch signaling in target cells of interest, including for the treatment of diseases characterized by a dysregulation of Notch signaling.
Type:
Application
Filed:
July 20, 2017
Publication date:
August 15, 2019
Applicants:
Fred Hutchinson Cancer Research Center, The Board of Trustees of The Leland Stanford Junior University
Inventors:
Irwin Bernstein, Vincent Luca, Kenan Christopher Garcia
Abstract: The current disclosure describes methods of expanding precursor cells for hematopoietic transplantation in subjects. The methods culture precursor cells in media containing an immobilized high molecular weight LILRB2 agonist or an LILRB2 agonist in combination with a Notch agonist. The expanded cells can be used to treat a variety of hematopoietic disorders.
Type:
Grant
Filed:
May 21, 2015
Date of Patent:
August 6, 2019
Assignees:
Fred Hutchinson Cancer Research Center, Board of Regents of the University of Texas System
Inventors:
Irwin D. Bernstein, Chengcheng Zhang, Mi Deng, Zhigang Lu, Junke Zheng
Abstract: Groups of bi-specific binding domain constructs (BS-BDC) to treat cancer are described. Each BS-BDC in a group targets a cancer antigen epitope and an immune cell activating epitope that is different from the cancer antigen epitope and immune cell activating epitope targeted by another BS-BDC in the group. The different cancer antigen epitopes can be on the same cancer antigen.
Type:
Application
Filed:
July 14, 2017
Publication date:
August 1, 2019
Applicant:
Fred Hutchinson Cancer Research Center
Inventors:
Christopher Mehlin, Colin Correnti, James Olson, Roland B. Walter, Ashok Bandaranayake, George S. Laszlo
Abstract: The present disclosure relates to immune cells that express an exogenous neoantigen and an immunogenicity enhancer, or to T cells that express an exogenous neoantigen, and their use in treating a disease or disorder, such as cancer for tumor associated neoantigens. Related expression constructs, kits, host cells, pharmaceutical compositions, and methods are also provided.
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: Multimerized human immunodeficiency virus (HIV) envelope glycoproteins are described. The envelope glycoproteins are multimerized Engineered and multimerized human immunodeficiency virus (HIV) envelope glycoproteins are described. The envelope glycoproteins can be multimerized using a heptamerization domain such as a C4b binding protein multimerization domain or a ferritin fusion. The engineered and multimerized envelope glycoproteins can derived from glycoprotein 120 (gp 120) and can used as an HIV vaccine.
Type:
Grant
Filed:
March 24, 2016
Date of Patent:
July 9, 2019
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Roland K. Strong, Colin Correnti, Leonidas Stamatatos, Andrew McGuire
Abstract: T cell receptors (TCRs) that have specificity for the WT1 antigen are provided. The TCRs include higher affinity TCRs that were engineered through the generation of mutational libraries of TCRs in a single-chain format, followed by selection for improved stability and affinity on the surface of yeast (i.e. directed evolution). In embodiments, the TCRs can be used in soluble form for targeted delivery in vivo, or as genes introduced into T cells in an adoptive T cell setting.
Type:
Grant
Filed:
November 21, 2014
Date of Patent:
July 9, 2019
Assignees:
THE BOARD OF TRUSTEES OF THE UNIVERSITY OF ILLINOIS, FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Sheena N. Smith, Daniel T. Harris, David M. Kranz, Philip D. Greenberg, Thomas M. Schmitt