Abstract: Polynucleotide molecules encoding CTCF are isolated and purified and sequenced. The CTCF proteins and antibodies thereto can be used to identify mutant CTCFs in methods of diagnosis.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
October 26, 1999
Assignees:
Fred Hutchinson Cancer Research Center, Cancer Research Campaign Technology, Ltd.
Inventors:
Victor L. Lobanenkov, Paul E. Neiman, Elena M. Klenova, Graham H. Goodwin, Galina N. Filippova, Steven J. Collins, Robert H. Nicolas
Abstract: Inhibitors of the p27 cyclin dependent kinase inhibitor protein or sequences encoding the protein modulate vertebrate cell cycle progression and increase the proportion of dividing cells to non-dividing cells in a population of treated cells. As the proportion of dividing cells increases, the cell population, e.g., hematopoietic progenitor (stem) cells, is more efficiently used for gene therapy applications.
Type:
Grant
Filed:
January 18, 1996
Date of Patent:
September 28, 1999
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
James M. Roberts, Steven R. Coats, Matthew L. Fero
Abstract: Canine granulocyte macrophage colony stimulating factor (caGM-CSF) corresponding to that found in canine serum and/or tissues, structural variants thereof, genes that encode these materials, related expression vectors and cells, recombinant methods for making caGM-CSF, and veterinary treatments therewith.
Abstract: A novel gene, Inhibitor of MyoD Family (I-mf), is provided which encodes novel proteins, I-mfa, I-mfb and I-mfc, involved in regulation of myogenesis during vertebrate development. I-mf is highly expressed in the sclerotome of developing vertebrates and is postulated to play an important role in patterning of the somite and determination sclerotomal cell fate. A unique, C-terminal interactional domain of the I-mf protein mediates physical interactions between I-mfa and members of the MyoD family of transcriptional activators and functions to inhibit transactivation of muscle specific genes by MyoD family members, thereby repressing myogenesis. Further characterization of I-mf activity shows that I-mf associates with MyoD family member proteins and retains them in the cytoplasm by masking their nuclear localization signals.
Type:
Grant
Filed:
August 27, 1996
Date of Patent:
March 23, 1999
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
C. M. Amy Chen, Norbert Kraut, Mark Groudine, Harold Weintraub, deceased
Abstract: Immortalized human stromal cell lines sustain and expand human hematopoietic precursor cells. The precursor cells are obtained from a blood product and inoculated into a culture medium conditioned by exposure to a human stromal cell line. Preferred human stromal cell lines secrete SCF, LIF, MIP1.alpha., and IL-6, as exemplified by a human stromal cell line designated HS-1. The conditioned culture medium may be supplemented with additional growth factors, such as interleukin-3. After expansion the human hematopoietic precursor cells are harvested and returned to a patient or frozen and stored. The immortalized human stromal cell lines can also be used as feeder layers in ex vivo bone marrow cultures or in colony forming assays.
Type:
Grant
Filed:
May 23, 1997
Date of Patent:
March 9, 1999
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Beverly Torok-Storb, Bryan A. Roecklein, Gretchen Johnson
Abstract: There is disclosed a method for screening for inhibitors of cellular second messenger signaling regulated by lysophosphatidic acid acyl transferase (LPAAT) and phosphatidic acid phosphohydrolase (PAPH), which method comprises contacting target cells or appropriate subcullular elements under appropriate conditions of stimulation with a candidate drug and assessing the levels of the relevant subsets of phosphatidic acid (PA) and diacylglycerol (DAG) in the presence and absence of the candidate drug.
Type:
Grant
Filed:
February 14, 1994
Date of Patent:
January 5, 1999
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
James A. Bianco, Stuart L. Bursten, Jack W. Singer
Abstract: This invention includes methods for increasing the efficiency of transduction of cells, including non-dividing cells, by recombinant AAV vectors. The methods utilize agents that alter certain aspects of DNA metabolism, more specifically, that affect DNA synthesis and/or affect repair, that impact on maintenance of chromosomal integrity, and/or that cause damage to the cellular DNA. Agents and vectors can now also be preselected and screened for transducing ability and/or transducing agents for their effect on DNA metabolism. These agents include tritiated nucleotides such as thymidine, gamma irradiation, UV irradiation, cis-platinum, etoposide, hydroxyurea and aphidicolin.
Type:
Grant
Filed:
February 25, 1997
Date of Patent:
November 10, 1998
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Ian E. Alexander, David W. Russell, A. Dusty Miller
Abstract: A substantially pure epinectin covalently linked glycoprotein complex is disclosed having a ligand portion binding at least to the .alpha..sub.3 .beta..sub.1 integrin receptor for use in modifying cellular adhesion to a substratum. Also disclosed are specific binding partners for epinectin, as exemplified by monoclonal antibody, and .alpha..sub.3 .beta..sub.1 and .alpha..sub.6 .beta..sub.4 integrin receptor peptides for use as inhibitors, antagonists, and agonists of receptor binding to epinectin ligand.
Abstract: Methods for establishing continuous SCF dependent lympho-hematopoietic progenitor cell lines capable of differentiating into erythroid, myeloid, and B lymphocytic lineages, and GM-CSF dependent neutrophil progenitor cell lines capable of differentiating into neutrophils but not into monocytes, mast cells, or basophils, by introducing into bone marrow, fetal spleen, fetal liver, or other hematopoietic myeloid cells nucleic acid encoding a dominant negative suppressor of a retinoic acid receptor-alpha and a selectable marker, and culturing the recombinant cells in culture medium containing SCF or GM-CSF, agents allowing for selective growth of the recombinant cells, and a level of retinoic acid of less than about 10.sup.-8 M to about 10.sup.-9 M in the case of establishing neutrophilic progenitor cell lines. Addition of a retinol compound induces the latter cell line to differentiate into neutrophils.
Abstract: A therapeutic method of modulating the immune response, by administering to a patient an amount of IL-4 effective to promote peripheral blood lymphocyte adhesion to microvascular endothelial cells in lymphoid organs. The IL-4 is preferably coadministered with IL-1.beta..An improved method of screening a cell line for the production of a binding partner that binds with a cell adhesion molecule, by contacting the binding partner with IL4-activated and nonactivated microvascular endothelial cells, and selecting binding partners that bind to the IL4-activated microvascular endothelial cells but not to the nonactivated microvascular endothelial cells. The selected binding partners may thereafter be tested for the ability to block lymphocyte binding to cytokine-activated endothelial cells. The binding partners are preferably also characterized by binding to human VCAM-1 and to IL4- or TNF.alpha.-activated bone marrow stromal cells. A representative embodiment is mAb 6G10 produced by hybridoma ATTC No. HB 10519.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
October 27, 1998
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Boris Masinovsky, William Michael Gallatin, Paul J. Simmons
Abstract: The present invention provides a rapid expansion method (termed "REM"), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes. REM involves culturing the T cells in association with a disproportionately large concentration of nondividing feeder cells, preferably .gamma.-irradiated peripheral blood mononuclear cells ("PBMC") present at an excess of at least 40-fold (relative to the number of target T cells), more preferably at an excess of at least about 200-fold. Cultures grown under REM exhibit dramatically enhanced expansion rates that can be even further elevated by the use of appropriate concentrations of an additional feeder cell, an anti-CD3 monoclonal antibody and IL-2, as described herein. Clonal expansions in the range of 500-fold to 3000-fold can be achieved within a single stimulation cycle of about 10-13 days, which is more than 100-fold more efficient than currently employed methods of culturing human T cell clones.
Type:
Grant
Filed:
October 3, 1994
Date of Patent:
October 27, 1998
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
Stanley R. Riddell, Philip D. Greenberg
Abstract: Nucleic acid molecules capable of hybridizing under stringent conditions to the nucleotide sequence residing between positions 1 and 1185 of the human cyclin E cDNA sequence shown in FIG. 2. Polypeptides encoded by such nucleic acid molecules, and immunologic binding partners directed to such polypeptides.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
September 15, 1998
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
James M. Roberts, Motoaki Ohtsubo, Andrew C. Koff, Frederick Cross
Abstract: Provided are methods of classifying and prognosticating human neuroectodermal tumors by analyzing a sample of the tumor to determine whether various bHLH proteins are detectably expressed in the sample. In the methods disclosed herein, expression of the bHLH genes is assessed by measuring transcripts or proteins expressed from the genes.
Abstract: Nucleic acid molecules capable of hybridizing under stringent conditions to the nucleotide sequence residing between positions 1 and 1185 of the human cyclin E cDNA sequence shown in FIG. 2. Polypeptides encoded by such nucleic acid molecules, and immunologic binding partners directed to such polypeptides.
Type:
Grant
Filed:
June 7, 1995
Date of Patent:
July 21, 1998
Assignee:
Fred Hutchinson Cancer Research Center
Inventors:
James M. Roberts, Motoaki Ohtsubo, Andrew C. Koff, Frederick Cross
Abstract: Retroviral packaging cells produce replication-defective retroviral vector particles capable of binding to Glvr-1 or Ram-1 retroviral receptors on target cells and are useful in gene therapy. The packaging cell employs a vector encoding a 10A1 retroviral env protein and produces the retroviral particles at high titer.
Abstract: Allogeneic cells are removed from an individual predisposed to or suffering from scleroderma or related diseases, thereby treating the disease and inhibiting or preventing its recurrence. Allogeneic cells are identified in the individual and treatment tailored to remove such cells, in vivo or ex vivo, from the individual by cell separation or cytotoxic agents.