Medium Contains An Interleukin Patents (Class 435/386)
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Patent number: 7029671Abstract: The invention relates to a method for activating human-derived antigen-presenting cells by in vitro cultivation with at least one of the glycoside compounds represented by formula (A) or salts thereof [preferred example: (2S,3S,4R)-1-(?-D-galactopyranosyloxy)-2-hexacosanoylamino-3,4-octadecanediol], and to human antigen-presenting cells activated by the method. The invention also relates to a method for treatment of cancer and infectious diseases including AIDS with the activated human antigen-presenting cells, and to a use of the activated human antigen-presenting cells in the preparation of medicines for treating such diseases. The invention can provide a satisfactory therapeutic effect on cancer and infectious diseases including AIDS without the need to pulse the human antigen-presenting cells with tumor antigens.Type: GrantFiled: November 27, 2000Date of Patent: April 18, 2006Assignee: Kirin Brewery Company, LimitedInventors: Yasuhiko Koezuka, Yasunori Yamaguchi, Kazuhiro Motoki
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Patent number: 6982168Abstract: The present invention relates to immortalized, malignant, human, adult prostate epithelial cell lines or cell lines derived therefrom useful in the diagnosis and treatment of prostate cancer. More particularly, the present invention relates to cloned, immortalized, malignant, human, adult prostate epithelial cell lines and uses of these cell lines for the diagnosis and treatment of cancer. Furthermore, the present invention provides for the characterization of said cell lines through the analysis of specific chromosomal deletions.Type: GrantFiled: January 30, 1997Date of Patent: January 3, 2006Assignee: The United States of America as represented by the Department of Health and Human ServicesInventors: Suzanne L. Topalian, W. Marston Linehan, Robert K. Bright, Cathy D. Vocke
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Patent number: 6969609Abstract: The present invention is a recombinant vector encoding and expressing at least three or more costimulatory molecules. The recombinant vector may additionally contain a gene encoding one or more target antigens or immunological epitope thereof. The synergistic effect of them costimulatory molecules on the enhanced activation of T cells is demonstrated. The degree of T-cell activation using recombinant vectors containing genes encoding three costimulatory molecules was far greater than the sum of recombinant vector constructs containing one costimulatory molecule and greater that the use of two costimulatory molecules. Results employing the triple costimulatory vectors were most dramatic under conditions of either low levels of first signal or low stimulator to T-cell ratios. This phenomenon was observed with both isolated CD4+and CD8+T cells.Type: GrantFiled: November 12, 1999Date of Patent: November 29, 2005Assignee: The United States of America as represented by the Department of Health and Human SerivcesInventors: Jeffrey Schlom, James Hodge, Dennis Panicali
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Patent number: 6960473Abstract: We describe a new two-step culture method for mass production in vitro of erythroid cells from either CD34+ (105 cells/mL) or light-density (106 cells/mL) cells purified from the blood of normal donors and thalassemic patients. The method includes (i) culture of the cells in the presence of dexamethasone and estradiol (10?6 M each) and (ii) the growth factors SCF (50 ng/mL), IL-3 (1 ng/mL), and EPO (1 U/mL). In their proliferative phase, these cultures generated about 1-2×107 erythroblasts for each milliliter of blood collected from normal donors or thalassemic patients. They were composed mostly (90%) of CD45low/glycophorin (GPA)neg/CD71low cells at day 7, 50-60% of which became CD45neg/GPA+/CD71high by days 15-20. However, when cells from days 7 to 12 of the proliferative phase were transferred in differentiation medium containing EPO and insulin, they progressed to mature erythroblasts (>90% benzidinepos and CD45neg/GPA+/CD71medium) in 4 days.Type: GrantFiled: February 26, 2004Date of Patent: November 1, 2005Assignee: Istituto Superiore di SanitaInventors: Giovanni Migliaccio, Anna Rita Franco
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Patent number: 6919206Abstract: Ligands for flt3 receptors capable of transducing self-renewal signals to regulate the growth, proliferation or differentiation of progenitor cells and stem cells are disclosed. The invention is directed to flt3-L as an isolated protein, the DNA encoding the flt3-L, host cells transfected with cDNAs encoding flt3-L, compositions comprising flt3-L, methods of improving gene transfer to a mammal using flt3-L, and methods of improving transplantations using flt3-L. Flt3 -L finds use in treating patients with anemia, AIDS and various cancers.Type: GrantFiled: December 19, 1997Date of Patent: July 19, 2005Assignee: Immunex CorporationInventors: Stewart D. Lyman, M. Patricia Beckmann
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Patent number: 6838081Abstract: The present invention provides methods for enhancing the development of APC from precursor cells by administering a combination of GM-CSF and IL-4. The precursor cells include: cells contained in peripheral blood, CD14+ cells and precursors in bone marrow. Thus, administration of GM-CSF and IL-4 can be used as a form of cytokine immunotherapy. One embodiment of the present invention involves systemic administration of GM-CSF and IL-4. In this embodiment, APC are required to directly access tumor antigens as they exist in vivo within the patient. A further embodiment of the present invention involves co-administration of a tumor-associated or tumor-specific antigen, with GM-CSF and IL-4, to induce antigen-specific immunity mediated by APC. Yet another embodiment of the present invention describes systemic administration of GM-CSF and IL-4 to achieve reduced tumor burden.Type: GrantFiled: April 2, 1999Date of Patent: January 4, 2005Assignee: The Regents of the University of CaliforniaInventors: Michael Derek Roth, Robert Alan Figlin, Sylvia Marie Kiertscher, Barbara Jennifer Gitlitz
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Patent number: 6828147Abstract: TALL-104 cells, and other cytotoxic T cell lines, may be modified to increase the cytotoxicity thereof, to enhance growth properties, and/or to provide a preferred phenotype, e.g., expression of cell surface antigens, function, e.g., change in cytokine production profile, by culturing the cells in an effective amount of IL-15, optionally followed by gamma irradiation to halt proliferation.Type: GrantFiled: August 21, 2001Date of Patent: December 7, 2004Assignee: The Wistar Institute of Anatomy and BiologyInventors: Daniela Santoli, Giovanni Rovera, Alessandra Cesano
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Patent number: 6805869Abstract: The present invention provides a method for enhancing the immunogenicity of weakly immunogenic or non-immunogenic cells, resulting in a cellular vaccine that can stimulate T cell activation, which in turn leads to an effective immune response. The cellular vaccines of the present invention are useful for the prevention and treatment of diseases which develop and/or persist by escaping the immune response triggered by T cell activation. Such diseases include, for example, all cancers, natural and induced immune deficiency states, and diseases caused by infections with a variety of pathogens.Type: GrantFiled: December 17, 1998Date of Patent: October 19, 2004Assignee: Shanghai CP Guojian Pharmaceutical Co., Ltd.Inventor: Yajun Guo
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Patent number: 6733746Abstract: The present invention provides a serum-free supplement which supports the growth of hematopoietic cells in culture. Also provided are a medium comprising a basal medium supplemented with the serum-free supplement of the present invention. The present invention also provides methods for culturing and for differentiating hematopoietic cells.Type: GrantFiled: January 31, 1997Date of Patent: May 11, 2004Assignee: Invitrogen CorporationInventors: John P. Daley, Barbara M. Dadey, William C. Biddle, Michelle G. Wysocki
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Patent number: 6692958Abstract: Activated lymphocytes derived from cord blood are excellently effective for preventing and treating various types of tumors and various types of infection. With interleukin 2 and/or anti-CD3 antibody, the lymphocytes derived from the cord blood is prepared by segregating lymphocytes from the cord blood and proliferating the segregated lymphocytes directly in vitro or segregating monocytes from cord blood and proliferating the monocytes in vitro. Also, the cord blood-derived activated lymphocytes can be effectively used for preventing recurrence of the diseases and promoting the take of stem cells or other organs.Type: GrantFiled: December 4, 2001Date of Patent: February 17, 2004Assignee: Humantec Ltd.Inventors: Teruaki Sekine, Kiminari Ito, Norio Shimizu, Kenzo Bamba, Tomohiro Yamaguchi, Yasuyuki Kuroiwa
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Publication number: 20040019390Abstract: The present invention relates, generally, to methods and compositions for allogeneic transplantation. More particularly, the invention relates to the use of alloreactive natural killer cells in order to enhance the efficacy and/or safety of allogeneic grafts in human subjects. The invention allows to increase the engraftment of an allogeneic grafts, even in myelo-reductive conditioning, to protect against GVHD and/or to eradicate malignant cells. The invention is particularly suited in allogeneic hematopoietic transplantations, particularly bone marrow transplantations.Type: ApplicationFiled: March 11, 2003Publication date: January 29, 2004Inventor: Andrea Velardi
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Patent number: 6667034Abstract: Methods, including culture media conditions, which provide for in vitro human stem cell division and/or the optimization of human hematopoietic progenitor cell cultures and/or increasing the metabolism or GM-CSF secretion or IL-6 secretion of human stromal cells and/or a method for assaying the effect of a substance or condition on a human hematopoietic cell population, and/or depleting the malignant cell or T-cell and B-cell content of a human hematopoietic cell population are disclosed. The methods rely on culturing human stem cells and/or human hematopoietic progenitor cells and/or human stromal cells in a liquid culture medium which is replaced, preferably perfused, either continuously or periodically, at a rate of 1 ml of medium per ml of culture per about 24 to about 48 hour period, and removing metabolic products and replenishing depleted nutrients while maintaining the culture under physiologically acceptable conditions. Optionally, growth factors are added to the culture medium.Type: GrantFiled: May 16, 1997Date of Patent: December 23, 2003Assignee: The Regents of the University of MichiganInventors: Bernhard O. Palsson, R. Douglas Armstrong, Michael F. Clarke, Stephen G. Emerson
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Patent number: 6645487Abstract: A method is described whereby dendritic cells derived from the CD34+ and CD 34-hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection.Type: GrantFiled: December 20, 2000Date of Patent: November 11, 2003Inventors: Cem Cezayirli, Mel Silvers
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Publication number: 20030134419Abstract: A method for producing proliferating cultures of dendritic cell precursors is provided. Also provided is a method for producing mature dendritic cells in culture from the proliferating dendritic cell precursors. The cultures of mature dendritic cells provide an effective means of producing novel T cell dependent antigens comprised of dendritic cell modified antigens or dendritic cells pulsed with antigen, including particulates, which antigen is processed and expressed on the antigen-activated dendritic cell. The novel antigens of the invention may be used as immunogens for vaccines or for the treatment of disease. These antigens may also be used to treat autoimmune diseases such as juvenile diabetes and multiple sclerosis.Type: ApplicationFiled: November 5, 2002Publication date: July 17, 2003Inventors: Ralph M. Steinman, Kayo Inaba, Gerold Schuler
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Patent number: 6586243Abstract: A method is described whereby dendritic cells derived from the CD34+ and CD 34− hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection.Type: GrantFiled: December 20, 2000Date of Patent: July 1, 2003Inventors: Cem Cezayirli, Mel Silvers
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Patent number: 6558949Abstract: This invention relates to media for culturing human cells that the proliferation speed of human cells is increased and the cell expression type is stably manifested, and to a method for culturing human cells using the same. This invention is characterized in that the media used for culturing human cells comprises human serum.Type: GrantFiled: December 13, 2000Date of Patent: May 6, 2003Inventors: Byoung-Hyun Min, So Ra Park
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Patent number: 6511848Abstract: A method for culturing and/or multiplying lymphocytes in cell culture medium which contains as lymphocyte growth factor and additionally, aurin tricarboxylic acid, ciclosporin, tacrolimus, and/or ascomycin.Type: GrantFiled: November 12, 1998Date of Patent: January 28, 2003Assignee: Winfried AlbertInventors: Herbert Jungfer, Heinrich Barchet, Winfried Albert
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Publication number: 20020182730Abstract: Compositions containing clinically relevant numbers of immune cells that have been isolated from a patient differentiated and/or expanded ex vivo. Methods for treating or preventing disease or otherwise altering the immune status of the patient by reinfusing such cells into the donor are also provided. Methods for expanding and/or immune cells, including effector cells, in the absence of exogenous IL-2, and for administering the cells in the absence of co-infused IL-2 are also provided.Type: ApplicationFiled: July 31, 1998Publication date: December 5, 2002Inventor: MICHEAL L. GRUENBERG
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Publication number: 20020182178Abstract: The invention relates to the use of IL-15 or active variants thereof and/or IL-15 activity enhancing compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system, such as manipulating viability ad/or responsiveness of said memory cells. The IL-15 activity enhancing compound is for example lipopolysaccharide (LPS). The invention further relates to the use of IL-15 inhibiting or eliminating compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system. Such inhibiting or eliminating compounds are for example anti-IL-15 antibodies, anti-IL-15R&agr; antibodies, fragments of these antibodies, e.g. the Fab or F(ab′)2 fragment, soluble IL-15R&agr;, fusion proteins consisting of soluble IL-15R&agr;, and Fc fragment, compounds, e.g. peptides, binding-and/or inhibiting functional IL-15 receptor, IL-15 antisense oligonucleotides.Type: ApplicationFiled: October 18, 2001Publication date: December 5, 2002Inventors: Johan Adriaan Marc Grooten, Hans Peter Raf Dooms, Walter Charles Fiers
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Patent number: 6432711Abstract: An embryonic stem cell which may be induced to differentiate homogeneously into a desired primary cell line. The embryonic stem cell may be engineered with DNA, which encodes a protein or polypeptide which promotes differentiation of the stem cell into a specific cell line, such as, for example, a neuronal cell line, a muscle cell line, or a hematopoietic cell line. The DNA may encode a transcription factor found in the particular cell line. In another alternative, a desired cell line is produced from embryonic stem cells by culturing embryonic stem cells under conditions which provide for a three-dimensional network of embryonic stem cells, and then stimulating embryonic stem cells with an agent, such as retinoic acid, or dimethylsulfoxide, which promotes differentiation of the embryonic stem cells into the desired cell line, such as, for example, a neuronal cell line, or a muscle cell line.Type: GrantFiled: November 1, 1994Date of Patent: August 13, 2002Assignee: Diacrin, Inc.Inventors: Jonathan H. Dinsmore, Judson Ratliff
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Patent number: 6355237Abstract: The present invention relates to methods for using various forms of a novel receptor expressed by hematopoietic and endothelial cells. An additional variant form of this receptor has been detected in brain cells and shown to bind to the obese gene product, leptin. Therefore, leptin may be used to stimulate the growth and development of receptor-positive hematopoietic and endothelial cells in vitro and in vivo. In addition, this receptor is selectively expressed in hematopoietic progenitor cells with long-term repopulating potential. Thus, agents that specifically bind to this receptor may be used to identify and isolate progenitor cells for a variety of clinical applications.Type: GrantFiled: March 20, 1996Date of Patent: March 12, 2002Assignee: Progenitor, Inc.Inventors: H. Ralph Snodgrass, Joseph Cioffi, Thomas Joel Zupancic, Alan Wayne Shafer
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Patent number: 6344192Abstract: The invention relates to the use of IL-15 or active variants thereof and/or IL-15 activity enhancing compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system, such as manipulating viability ad/or responsiveness of said memory cells. The IL-15 activity enhancing compound is for example lipopolysaccharidc (LPS). The invention further relates to the use of IL-15 inhibiting or eliminating compounds for the manufacture of a pharmaceutical composition for manipulating memory cells of the immune system. Such inhibiting or eliminating compounds are for example anti-IL-15 antibodies, anti-IL-15R&agr; antibodies, fragments of these antibodies, e.g. the Fab or F(ab′)2 fragment, soluble IL-15R&agr;, fusion proteins consisting of soluble IL-15R&agr;, and Fc fragment, compounds, e.g. peptides, binding and/or inhibiting functional IL-15 receptor, IL-15 antisense oligonucleotides.Type: GrantFiled: August 23, 1999Date of Patent: February 5, 2002Assignee: Vlaams Interuniversitair Instituut voor BiotechnologieInventors: Johan Adriaan Marc Grooten, Hans Peter Raf Dooms, Walter Charles Fiers
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Patent number: 6316257Abstract: The present invention provides a modified rapid expansion method (termed “low-PBMC-REM” or “modified-REM”), for quickly generating large numbers of T lymphocytes, including cytolytic and helper T lymphocytes, without using the large excesses of peripheral blood mononuclear cells (PBMC) or EBV-transformed lymphoblastoid cells (LCL) characteristic of high-PBMC-REM. Clonal expansions of greater than 500-fold can be achieved within a single stimulation cycle of about 8-14 days.Type: GrantFiled: March 3, 1997Date of Patent: November 13, 2001Assignee: Targeted Genetics CorporationInventors: David C. Flyer, Kim W. Clary
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Publication number: 20010033835Abstract: The present invention provides a serum-free supplement which supports the growth of hematopoietic cells in culture. Also provided are a medium comprising a basal medium supplemented with the serum-free supplement of the present invention. The present invention also provides methods for culturing and for differentiating hematopoietic cells.Type: ApplicationFiled: January 31, 1997Publication date: October 25, 2001Inventors: JOHN P. DALEY, BARBARA M. DADEY, WILLIAM C. BIDDLE, MICHELLE G. WYSOCKI
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Patent number: 6251665Abstract: A method is described whereby dendritic cells derived from the CD34+ and CD34− hematopoietic cell lineages are directed to become programmable antigen presenting cells. The programmed cells may be pulsed with tumor cell RNA or tumor cell RNA expression products. The protocol provides for directing the maturation of dendritic cells to become antigen presenting cells. The protocol further provides for isolating tumor cell RNA from biopsy material that has been prepared in paraffin block storage. The directed dendritic cell is provided with a plurality of tumor markers by using tumor RNA in toto, the poly A+RNA fraction or the expression product of such RNA. Once activated the dendritic cells are incubated with T4 and T8 lymphocytes to stimulate and sensitize the T lymphocytes which upon introduction either into a donor host or a nondonor recipient will provide immune response protection.Type: GrantFiled: February 3, 1998Date of Patent: June 26, 2001Inventors: Cem Cezayirli, Mel Silvers
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Patent number: 6251671Abstract: The invention relates to cell proliferation, cell differentiation, male infertility, male fertility and to compositions and methods involved therein. Also methods of culturing spermatogonial stem cells with bone morphogenetic protein 8 are disclosed.Type: GrantFiled: February 28, 1997Date of Patent: June 26, 2001Assignee: Vanderbilt UniversityInventors: Brigid L. M. Hogan, Guang-Quan Zhao
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Patent number: 6165785Abstract: A method of treatment using immune system suppressor cells and immune system stimulator cells comprises providing stem cells; combining the stem cells with lymphoid-derived cells to produce a co-culture; adding lipopolysaccharide and a factor selected from the group consisting of granulocyte macrophage-colony stimulating factor, macrophage colony stimulating factor, granulocyte-colony stimulating factor and mixtures thereof to the co-culture; obtaining immune system suppressor cells and immune system stimulator cells from the co-culture; and introducing and the cells into a host.Type: GrantFiled: October 23, 1998Date of Patent: December 26, 2000Assignees: University of Cincinnati, Shriners Hospitals for ChildrenInventors: Cora K. Ogle, John F. Valente, J. Wesley Alexander
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Patent number: 6114168Abstract: A culture medium for culturing chicken embryonic stem (ES) cells is disclosed. The culture medium is used for supporting avian ES cell cultures. The components of the avian ES cell media include cytokines, fibroblast growth factors, insulin-like growth factors and stem cell growth factors and anti-retinoic acid antibody. The culture medium is substantially free of active retinoic acid. A method for culturing avian ES cells and the resulting products are also disclosed.Type: GrantFiled: May 12, 1997Date of Patent: September 5, 2000Assignees: Institute National de la Recherche Agronomique, Centre National de la Recherche Scientifique (CNRS), Ecole Normale Superieure de LyonInventors: Jacques Samarut, Bertrand Pain
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Patent number: 6110739Abstract: The present invention relates to novel immortalized precursor cell populations derived from embryonic stem cell populations and methods to produce such cell populations. Also disclosed is an assay to identify regulatory compounds capable of controlling cell growth for therapeutic and experimental use.Type: GrantFiled: February 22, 1999Date of Patent: August 29, 2000Assignee: National Jewish Medical and Research CenterInventors: Gordon M. Keller, Robert G. Hawley, Kyunghee Choi
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Patent number: 6077519Abstract: Methods are provided for eluting peptides that are bound to major histocompatibility complex ("MHC") molecules expressed on the cell surfaces of viable cells that have at least one MHC-peptide complex on the surfaces of the cells. Methods are provided for using such acid-eluted T cell epitopes, preferably obtained from a patient's tumor, and autologous dendritic cells as the basis for antitumor vaccines.Type: GrantFiled: January 15, 1997Date of Patent: June 20, 2000Assignee: University of PittsburghInventors: Walter J. Storkus, Michael T. Lotze
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Patent number: 6004812Abstract: The present invention provides an in vitro T-lymphopoiesis system in which a population of T-cells is produced from precursor cells expressing CD34. The T-lymphopoiesis system of the present invention produces a population of T-cells of which approximately 17-74% express CD2, approximately 1.5-34% express CD3, and approximately 16-61% express CD4, and approximately 0-15% express CD8. A method of producing such a population of T-cells in vitro, as well as various compositions including T-cells of the present invention, are also provided.Type: GrantFiled: August 11, 1998Date of Patent: December 21, 1999Assignee: Beth Israel Medical Center, Inc.Inventors: David T. Scadden, Andrew Freedman
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Patent number: 5958774Abstract: A method is disclosed for gene transfer into a culture of primitive stem cells which comprises a prestimulation step of adding a blocking agent to block at least one inhibitor of a cell cycle of said primitive stem cells. The prestimulation is time-limited for a period of less than approximately 36 hours so that said culture of primitive stem cells retains hematopoietic potential.Type: GrantFiled: July 10, 1997Date of Patent: September 28, 1999Assignee: Centre National de la Recherche ScientifiqueInventors: Antoinette Klein, Jacques Hatzfeld
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Patent number: 5928639Abstract: Methods have been discovered for treating minimal residual disease following removal of most or a substantial fraction of malignant cells from a cancer patient. An autologous stem cell transplant is performed on the patient. Following partial hematopoiesis recovery, the patient is infused with allogeneic peripheral blood lymphocytes, either alone or in combination with in vivo or in vitro cytokine. The infused allogeneic lymphocytes engender an anti-malignant cell response and can be instrumental in prevention of disease relapse.Type: GrantFiled: October 23, 1996Date of Patent: July 27, 1999Assignee: Hadasit Medical Research Services and Development Ltd.Inventor: Shimon Slavin
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Patent number: 5919700Abstract: The invention relates to a method of stimulating the proliferation of natural killer cells with in vitro IL-16. A mixed lymphocyte cell population which contains natural killer cells can be nylon wool-purified, and cultured in the presence of an effective amount of IL-16 to stimulate the proliferation of natural killer cells. Effective concentrations of IL-16 which enhance the proliferation of natural killer cells range from 1 ng/ml to 1000 ng/ml. Both the full length IL-16 protein or the naturally occurring carboxy terminal-truncated form of IL-16 are suitable for stimulating the proliferation of the natural killer cells. The IL-16 induced proliferation results in at least a five-fold enrichment of natural killer cells, and the natural killer cells can be subsequently isolated from the mixed lymphocyte culture.Type: GrantFiled: August 23, 1996Date of Patent: July 6, 1999Assignee: MCW Research FoundationInventors: Ernest C. Borden, Jonathan D'Cunha
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Patent number: 5914268Abstract: The present invention relates to novel pluripotent embryonic cell populations derived from embryonic stem cell populations and methods to produce such pluripotent embryonic cell populations. Disclosed is an embryonic stem cell-derived pluripotent embryoid body cell population having one or more cells capable of developing into cells of hematopoietic and/or endothelial lineage. Also disclosed is an embryoid body cell population-derived mixed population of endothelial and erythroid cells. Also disclosed is an embryoid body cell population-derived embryonic blast cell population capable of developing into a variety of hematopoietic cell types. The invention is additionally directed to embryonic stem cell population-derived T and B cell populations. Methods to identify embryonic cell compounds are also disclosed for therapeutic and experimental use.Type: GrantFiled: November 21, 1994Date of Patent: June 22, 1999Assignee: National Jewish Center for Immunology & Respiratory MedicineInventors: Gordon M. Keller, Marion Kennedy, Kyunghee Choi, Meri T. Firpo
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Patent number: 5874301Abstract: The present invention relates to novel immortalized precursor cell populations derived from embryonic stem cell populations and methods to produce such cell populations. Also disclosed is an assay to identify regulatory compounds capable of controlling cell growth for therapeutic and experimental use.Type: GrantFiled: December 11, 1995Date of Patent: February 23, 1999Assignee: National Jewish Center for Immunology and Respiratory MedicineInventors: Gordon M. Keller, Robert G. Hawley, Kyunghee Choi
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Patent number: 5874308Abstract: Methods and compositions are provided for in vitro expansion of growth factor dependent cells. Expansion is effected through the use of growth factor conjugates that include a growth factor such as a steel factor and a polysaccharidase substrate binding region. The conjugates are immobilized by binding of the substrate binding region to a substrate of the polysaccharidase in a growth chamber for the cells.Type: GrantFiled: January 16, 1996Date of Patent: February 23, 1999Assignee: University of British ColumbiaInventors: Douglas G. Kilburn, Keith R. Humphries, James G. Doheny, Eric Jervis, Judie Alimonti
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Patent number: 5861315Abstract: Stem cell factor in combination with soluble interleukin-6 receptor, interleukin-6, for gp130 signaling, supports the proliferation, differentiation and terminal maturation of blood cells from normal human hematopoietic multipotential cells.Type: GrantFiled: October 16, 1996Date of Patent: January 19, 1999Assignees: Amgen Inc., Tosoh CorporationInventor: Tatsutoshi Nakahata
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Patent number: 5846827Abstract: Methods for activating cytotoxic T lymphocytes (CTL) in vitro are presented in conjunction with methods for using the activated CTL for therapy in vivo. Additionally, a method for killing specific CTL in vivo is presented using antigen presenting cells which were modified in vitro.Type: GrantFiled: June 6, 1995Date of Patent: December 8, 1998Assignee: Cytel CorporationInventors: Esteban Celis, Ralph Kubo, Horacio Serra, Van Tsai, Peggy Wentworth
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Patent number: 5830464Abstract: The present invention relates to methods and compositions for eliciting an immune response and the prevention and treatment of primary and metastatic neoplastic diseases and infectious diseases. The methods of the invention comprise administering a composition comprising an effective amount of a complex, in which the complex consists essentially of a heat shock protein (hsp) noncovalently bound to an antigenic molecule in combination with administering antigen presenting cells sensitized with complexes of hsps noncovalently bound to an antigenic molecule. "Antigenic molecule" as used herein refers to the peptides with which the hsps are endogenously associated in vivo as well as exogenous antigens/immunogens (i.e., with which the hsps are not complexed in vivo) or antigenic/immunogenic fragments and derivatives thereof. In a preferred embodiment, the complex is autologous to the individual. In a specific embodiment, the effective amounts of the complex when administered intradermally are in the range of 0.Type: GrantFiled: February 7, 1997Date of Patent: November 3, 1998Assignee: Fordham UniversityInventor: Pramod K. Srivastava
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Patent number: 5827642Abstract: 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: GrantFiled: October 3, 1994Date of Patent: October 27, 1998Assignee: Fred Hutchinson Cancer Research CenterInventors: Stanley R. Riddell, Philip D. Greenberg
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Patent number: 5811301Abstract: In vitro production of clinically useful quantities of single species of mature, differentiated human blood cells is carried out by a method in which human pluripotent hematopoietic stem cells, preferably from a universal donor, are incubated in a bioreactor in a growth medium also containing specific combinations of recombinant human growth and maturation promoting polypeptide factors that expand stem cell cultures and promote the maturation and differentiation of stem cells into single species of erythroid, thrombocytic or granulocytic human blood cells, and harvesting the mature cells. The growth and maturation promoting polypeptides employed include SCGF, Interleukins 1,3,4,5,6, and 11, GM-CSF, M-CSF, G-CSF and EPO. Stem cells may be preliminarily genetically modified so as to remove histocompatibility or blood group antigens with which a recipient may be incompatible, or the stem cells may be genetically altered by transfection with appropriate DNA-containing vectors, prior to addition to the bioreactor.Type: GrantFiled: August 7, 1996Date of Patent: September 22, 1998Inventor: Robert B. Cameron
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Patent number: 5807744Abstract: The invention provides a method for inhibition of proliferation of primitive hematopoietic progenitor cells and hematopoietic stem cells, by incubating preparations containing said cells with IFN-.gamma.. The method is especially useful for protecting said cells during purging techniques using cytotoxic treatment, and for protection of said cells during in vivo cytotoxic treatment.Type: GrantFiled: August 14, 1995Date of Patent: September 15, 1998Assignee: Boehringer Mannheim GmbHInventors: Zwi Berneman, Dirk Van Bockstaele, Hans-Willem Snoeck
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Patent number: 5780301Abstract: Disclosed is a synthetic medium with PDGF, vitronectin, IL-1.beta. and BSA added to Eagle's minimum essential medium or medium with transferrin, insulin, progesterone and putrescine further added thereto. When cultivating the postnatal central neurons using the inventive medium, there are effects such that good attachment to substrate, extension of neuritic processes and maintenance of survival are achieved, that more stable sure cultivation becomes possible as well over the astrocyte-conditioned medium used hitherto, and the like.Type: GrantFiled: February 13, 1995Date of Patent: July 14, 1998Assignee: Kyorin Pharmaceutical Co., Ltd.Inventors: Hiroshi Saito, Hiroshi Katsuki, Fumio Kawahara
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Patent number: 5766944Abstract: A procedure for carrying out T cell differentiation of CD34+ stem cells in an in vitro culture of thymic epithelial fragments whereby the differentiated T cells achieve full immunocompetence. The invention also includes the procedure for differentiation of stem cells from HIV seropositive individuals or genetically modified stem cells. The invention broadly relates to the culture of cultured thymic epithelial fragments and provides procedures for verifying true immunocompetence of the resulting T cells and for analyzing the effects of various compounds on the differentiation process. The invention also comprises several novel applications for utilizing the procedure of the invention, including grafting fortified cultured thymic epithelial fragments and infusing immunocompetent T cells into patients with compromised immune systems.Type: GrantFiled: December 31, 1996Date of Patent: June 16, 1998Inventor: Margaret Eileen Ruiz
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Patent number: 5759856Abstract: Disclosed is a method for the culture of higher eukaryotic cells which are dependent for survival on an exogenous factor. The method involves co-culturing the factor-dependent cells with an immortalized eukaryotic cell that has been engineered to secrete the requisite factor.Also disclosed is a cell line of non-stromal cell origin which secretes interleukin-7.Type: GrantFiled: June 7, 1995Date of Patent: June 2, 1998Assignee: Benjamin E. RichInventors: Philip Leder, Benjamin E. Rich
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Patent number: 5744361Abstract: The use of individual or combinations of cytokines, particularly IL-3, GM-CSF, and c-kit ligand are employed for long-term hematopoiesis in serum free culture in the absence of stromal cells. The cultures can be used for evaluating compounds and their effect on hematopoiesis, particularly as to lifetime and nature of differentiation. In addition, the expanded cells may be used for engraftment in a mammalian host or enhancement of particular cell lineages in a mammalian host. The subject systems may be used with any mammalian hemopoietic cells, but finds particular application with primates, more particularly humans.Type: GrantFiled: June 6, 1995Date of Patent: April 28, 1998Assignee: Indiana UniversityInventors: Ronald Hoffman, John Brandt
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Patent number: 5705162Abstract: The present invention broadly relates to a therapeutic agent effective in mitigating disease associated with Feline Leukemia Virus (FeLV) in a feline infected with FeLV. A feline is an animal of the family Felidae. The novel therapeutic agent is composed of feline excised lymph nodes which have been subjected to mitogenic stimulation for their expansion dispersed in a pharmaceutically-acceptable carrier. Mitogenic stimulation conditions include culturing the excised lymph nodes in the presence of Interleukin-2. Optionally, culture conditions can include the presence of allogeneic or autologous FeLV tumor. The inventive therapeutic agent is prepared by excising lymph nodes from a feline infected the FeLV, mitogenically stimulating said excised lymph nodes for their expansion, and administering to the infected feline the expanded lymph nodes. Multidose regimens can be used as is necessary or desirable in convenient fashion.Type: GrantFiled: October 16, 1995Date of Patent: January 6, 1998Assignee: Parhelion CorporationInventors: Richard G. Olsen, John L. Ridihalgh
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Patent number: 5633162Abstract: A biochemically defined culture medium for culturing engineered Chinese hamster ovary (CHO) cell lines, which is essentially free from protein, lipid and carbohydrate isolated from an animal source, having water, an osmolality regulator, a buffer, an energy source, amino acids including L-glutamine, an inorganic or recombinant iron source, and a synthetic or recombinant growth factor, and optionally non-ferrous metal ions vitamins and cofactors. Also cells adapted to grow in such a culture medium.Type: GrantFiled: March 4, 1994Date of Patent: May 27, 1997Assignee: Glaxo Wellcome Inc.Inventors: Michael J. Keen, Nicholas T. Rapson
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Patent number: 5610056Abstract: Stem cell factor in combination with interleukin-6 and soluble interleukin-6 receptor supports proliferation, differentiation and terminal maturation of erythroid cells from normal human hematopoietic stem cells.Type: GrantFiled: November 16, 1994Date of Patent: March 11, 1997Assignees: Amgen Inc., Tosoh CorporationInventor: Tatsutoshi Nakahata