Abstract: Systems and methods to increase the efficacy of vaccines that require or are rendered more effective with T cell mediated immunity are described. The systems and methods utilize polynucleotides that genetically modify T cells to express a T cell receptor specific for an administered vaccine antigen.
Abstract: The present invention relates to methods of treating immune disorders, particularly autoimmune and inflammatory disorders such as rheumatoid arthritis, and methods of producing antibodies for use in therapeutic strategies for treating such disorders. Generally, the present methods involve the use of antibodies that specifically bind to NKG2D receptors present on the surface of cells underlying the disorders.
Abstract: Provided are compositions and methods for the treatment of hemoglobinopathies such as thalassemias and sickle cell disease. Compositions and methods include one or more endonuclease(s) or endonuclease fusion protein(s), including one or more homing endonuclease(s) and/or homing endonuclease fusion protein(s) and/or CRISPR endonuclease(s) and/or CRISPR endonuclease fusion protein(s): (a) to disrupt a Bcl11a coding region; (b) to disrupt a Bcl11a gene regulatory region; (c) to modify an adult human ?-globin locus; (d) to disrupt a HbF silencing DNA regulatory element or pathway, such as a Bcl11a-regulated HbF silencing region; (e) to mutate one or more ?-globin gene promoter(s) to achieve increased expression of a ?-globin gene; (f) to mutate one or more ?-globin gene promoter(s) to achieve increased expression of a ?-globin gene; and/or (g) to correct one or more ?-globin gene mutation(s).
Type:
Grant
Filed:
March 16, 2017
Date of Patent:
April 14, 2020
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Ryo Takeuchi, Mark T Groudine, Barry L. Stoddard, Michael A Bender
Abstract: The present disclosure provides a panel of nucleic acid molecule primers specific for HLA-specific alleles and other genetic polymorphisms, which are useful for quantitatively amplifying these markers to detect, diagnose, and monitor individuals who have or are at risk of certain disease conditions, such as autoimmune disease, proliferative disease, infectious disease, allograft rejection, or pregnancy-related pathologies.
Type:
Grant
Filed:
March 1, 2013
Date of Patent:
March 31, 2020
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
J. Lee Nelson, Nathalie C. Lambert, Vijayakrishna K. Gadi, Zhen Yan
Abstract: Circular handed alpha-helical repeat proteins are described. The repeat proteins have a number of uses as scaffolds for geometrically precise, arrayed presentation of cell-signaling or immune-related protein and peptide epitopes, as well as numerous other therapeutic, diagnostic, and nanotechnological uses.
Abstract: Transposase-based barcoding of DNA for improved efficiency, high-accuracy sequencing is described. Transposases including transposable barcodes can be used to fragment and barcode target DNA in a single step.
Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.
Abstract: The present invention relates to methods and compositions for providing hematopoietic function to human patients in need thereof, by selecting a pool of expanded human cord blood stem/progenitor cell samples for administration to the patient, wherein the samples in the pool collectively do not mismatch the patient at more than 2 of the HLA antigens or alleles typed in the patient; and administering the selected pool of expanded human cord blood stem/progenitor cell samples to the patient. Methods for obtaining the pools of expanded human cord blood stem/progenitor cell samples, banks of frozen pools of expanded human umbilical cord blood stem/progenitor cell samples, and methods for producing such banks are also provided herein.
Abstract: The present disclosure provides compositions and methods for targeting a minor histocompatibility (H) antigen (HA-1H) to, for example, prevent or manage relapse of a hematological malignancy after allogeneic hematopoietic stem cell transplantation (HCT). Also provided are transgene constructs encoding engineered binding proteins, such as a T cell receptor or a chimeric antigen receptor, optionally encoding additional components such as a co-receptor and/or safety switch. Such transgene constructs can be transduced into an immune cell, such as a T cell, and used as an immunotherapy in a subject having a hematological malignancy or at risk for recurrence of the hematological malignancy (e.g., leukemia, lymphoma, myeloma).
Type:
Grant
Filed:
March 22, 2019
Date of Patent:
January 21, 2020
Assignee:
FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Marie Bleakley, Robson Dossa, Daniel Sommermeyer
Abstract: The present disclosure provides high affinity and enhanced affinity T cell receptors specific for human Wilms tumor protein 1 (WT-1) epitopes for use in treating diseases or disorders, such as cancer cells that overexpress WT-1.
Type:
Grant
Filed:
July 30, 2015
Date of Patent:
January 21, 2020
Assignee:
FRED HUTCHINSON CANCER RESEARCH CENTER
Inventors:
Thomas M. Schmitt, Philip D. Greenberg, Hieu Nguyen
Abstract: The present disclosure relates to compositions and methods for detecting rare nucleic acid molecule mutations in a plurality of nucleic acid molecules. Also disclosed are methods for determining the size of a nucleic acid molecule using droplet digital PCR.
Type:
Grant
Filed:
May 29, 2013
Date of Patent:
January 21, 2020
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Jason H. Bielas, Sean D. Taylor, Matthew T. Laurie
Abstract: The present disclosure pertains generally to double-stranded small interfering RNAs that modulate gene expression for use in research, diagnostics, and/or therapeutics. In certain embodiments, the present disclosure provides double-stranded small interfering RNAs that modulate DUX4 gene expression. In certain embodiments, the present disclosure provides methods of inhibiting DUX4 gene expression by contacting a cell with double-stranded small interfering RNAs.
Type:
Grant
Filed:
January 15, 2016
Date of Patent:
January 21, 2020
Assignees:
Ionis Pharmaceuticals, Inc., Fred Hutchinson Cancer Research Center
Abstract: In vivo gene therapies for immune deficiencies are described. The in vivo gene therapies utilize a foamy viral vector including a PGK promoter with a therapeutic gene. The foamy viral vector can be beneficially administered with cell mobilization into the peripheral blood.
Type:
Application
Filed:
February 15, 2018
Publication date:
January 9, 2020
Applicants:
Fred Hutchinson Cancer Research Center, Seattle Children's Hospital d/b/a Seattle Children's Research Institute
Inventors:
Frieda Chan, Olivier Humbert, Hans-Peter Kiem, Jennifer E. Adair, David Rawlings, Andrew Scharenberg, Troy Torgerson
Abstract: Systems and methods to expand hematopoietic stem cell (HSC) using zwitterionic hydrogels (ZTG) are described. Expansion using the disclosed systems and methods results in HSC populations with (i) an increased proportion of HSC versus partially or fully differentiated cells, (ii) proportionally lower cell surface expression levels of differentiation/maturation markers, (iii) reduced metabolic rates following expansion, and/or (iv) a greater proportion of quiescent cells following expansion, as compared to currently available clinical expansion methods.
Abstract: Systems and methods to modulate the function of mucosal-associated invariant T (MAIT) cells in the absence of a T cell receptor (TCR) signal are described. The systems and methods can be used to elucidate the function of MAIT cells to assess potential therapeutic strategies for conditions associated with inflammation.
Type:
Application
Filed:
January 23, 2018
Publication date:
December 19, 2019
Applicant:
Fred Hutchinson Cancer Research Center
Inventors:
Martin Prlic, Julia Berkson, Chloe Slichter
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 tagged chimeric effector molecules and receptor molecules thereof for genetically engineering a host cell, wherein the recombinant host cell can be identified, isolated, sorted, induced to proliferate, tracked or eliminated using the tag. An exemplary receptor molecule is a chimeric antigen receptor (CAR) having an extracellular domain comprising a binding domain for a target, a hinge region, and a tag cassette, a hydrophobic portion as a transmembrane domain and an intracellular part with an effector domain. An exemplary target is CD19. An exemplary tag is a Strep TagĀ®. T cells recombinantly modified for expression of such molecules may be used in adoptive immunotherapy.
Abstract: The present disclosure relates to compositions and methods for randomly introducing codon-mutations in a target nucleic acid molecule and, more particularly, using wild-type and triplet-randomized oligonucleotides to introduce mutations uniformly across a target nucleotide of interest in a controlled fashion and with a low rate of insertions or deletions.
Abstract: Strategies to assess and/or produce cell populations with predictive engraftment potential are described. The cell populations can be used for a variety of therapeutic and research purposes.
Type:
Application
Filed:
June 16, 2017
Publication date:
November 14, 2019
Applicant:
Fred Hutchinson Cancer Research Center
Inventors:
Stefan Radtke, Hans-Peter Kiem, Jennifer E. Adair
Abstract: The present invention relates to methods, kits and compositions for expansion of embryonic hematopoietic stem cells and providing hematopoietic function to human patients in need thereof. In one aspect, it relates to kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. Also provided herein are methods for expanding embryonic hematopoietic stem cells using kits and compositions comprising a Notch agonist, one or more growth factors, and, optionally, an inhibitor of the TGF? pathway. The embryonic hematopoietic stem cells expanded using the disclosed kits, compositions and methods include cells derived from an embryo (e.g., aorta-gonad-mesonephros region of the embryo), embryonic stem cells, induced pluripotent stem cells, or reprogrammed cells of other types.