11003results about "Blood/immune system cells" patented technology

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and stimulate cells that maximizes stimulation and / or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and / or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and / or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

The present invention relates generally to methods for stimulating cells, and more particularly, to a novel method to concentrate and / or stimulate cells that maximizes stimulation and / or proliferation of such cells. In the various embodiments, cells are stimulated and concentrated with a surface yielding enhanced proliferation, cell signal transduction, and / or cell surface moiety aggregation. In certain aspects methods for stimulating a population of cells such as T-cells, by simultaneous concentration and cell surface moiety ligation are provided by contacting the population of cells with a surface, that has attached thereto one or more agents that ligate a cell surface moiety and applying a force that predominantly drives cell concentration and cell surface moiety ligation, thereby inducing cell stimulation, cell surface moiety aggregation, and / or receptor signaling enhancement. Also provided are methods for producing phenotypically tailored cells, including T-cells for the use in diagnostics, drug discovery, and the treatment of a variety of indications, including cancer, viral infection, and immune related disorders. Compositions of cells having specific phenotypic properties produced by these processes are further provided.

Methods for inducing a population of T cells to proliferate by activating the population of T cells and stimulating an accessory molecule on the surface of the T cells with a ligand which binds the accessory molecule are described. T cell proliferation occurs in the absence of exogenous growth factors or accessory cells. T cell activation is accomplished by stimulating the T cell receptor (TCR) / CD3 complex or the CD2 surface protein. To induce proliferation of an activated population T cells, an accessory molecule on the surface of the T cells, such as CD28, is stimulated with a ligand which binds the accessory molecule. The T cell population expanded by the method of the invention can be genetically transduced and used for immunotherapy or can be used in methods of diagnosis.

The present invention relates to a genetically engineered, CD19-specific chimeric T cell receptor and to immune cells expressing the chimeric receptor The present invention also relates to the use of such cells for cellular immunotherapy of CD9+ malignancies and for abrogating any untoward B cell function. The chimeric receptor is a single chain scFvFc:ζ receptor where scFvFc designates the extracellular domain, scFv designates the VH and VL chains of a single chain monoclonal antibody to CD19, Fc represents at least part of a constant region of an IgG1, and ζ represents the intracellular signaling domain of the zeta chain of human CD3. The extracellular domain scFvFc and the intracellular domain ζ are linked by a transmembrane domain such as the transmembrane domain of CD4. In one aspect, the chimeric receptor comprises amino acids 23-634 of SEQ I DNO:2. The present invention further relates to a method of making a redirected T cell expressing a chimeric T cell receptor by electroporation using naked DNA encoding the receptor.

An embodiment of the invention provides a method of promoting regression of cancer in a mammal comprising obtaining a tumor tissue sample from the mammal; culturing the tumor tissue sample in a first gas permeable container containing cell medium therein; obtaining tumor infiltrating lymphocytes (TIL) from the tumor tissue sample; expanding the number of TIL in a second gas permeable container containing cell medium therein using irradiated allogeneic feeder cells and / or irradiated autologous feeder cells; and administering the expanded number of TIL to the mammal. Methods of obtaining an expanded number of TIL from a mammal for adoptive cell immunotherapy are also provided.

Integration of costimulatory signaling domains within a tumor targeting chimeric antigen receptor (CAR), such as the IL13Rα2 specific IL13-zetakine (IL13ζ), enhances T cell-mediated responses against tumors even in the absence of expressed ligands for costimulatory receptors.

The invention relates to methods and compositions for the differentiation of stromal cells from adipose tissue into hematopoietic supporting stromal cells and myocytes of both the skeletal and smooth muscle type. The cells produced by the methods are useful in providing a source of fully differentiated and functional cells for research, transplantation and development of tissue engineering products for the treatment of human diseases and traumatic tissue injury repair.

The invention provides a method of promoting regression of a cancer in a mammal comprising (i) culturing autologous T cells; (ii) expanding the cultured T cells; (iii) administering to the mammal nonmyeloablative lymphodepleting chemotherapy; and (iv) after administering nonmyeloablative lymphodepleting chemotherapy, administering to the mammal the expanded T cells, wherein the T cells administered to the mammal are about 19 to about 35 days old and have not been screened for specific tumor reactivity, whereupon the regression of the cancer in the mammal is promoted.

A method and system to protect users against potentially fraudulent activities associated with spoof web sites are described. According to one aspect of the present invention, the URL of a document downloaded via a web browser client is compared to the URLs in a list of URLs for known spoof sites. If the URL for the downloaded document is found in the list of URLs for known spoof sites, a security indicator is displayed to the user to indicate to the user that the downloaded document is associated with a known spoof site. According to another aspect of the invention, a security server maintains a master black list and periodically communicates updates of the master black list to the local list of a client security application.

The invention provides systems and methods for the generation of lymphocytes having a unique antigen specificity. In a preferred embodiment, the invention provides methods of virally infecting cells from bone marrow with one or more viral vectors that encode antigen-specific antibodies for the production of, for example B cells and T cells. In some embodiments, the viral vectors include an IRES or 2A element to promote separation of, for example, the α subunit and β subunit of a T cell receptor (TCR) or heavy and light chains of a B-cell antibody. The resulting lymphocytes, express the particular antibody that was introduced in the case of B cells and TCR in the case of T cells. The lymphocytes generated can be used for a variety of therapeutic purposes including the treatment of various cancers and the generation of a desired immune response to viruses and other pathogens. The resulting cells develop normally and respond to antigen both in vitro and in vivo. We also show that it is possible to modify the function of lymphocytes by using stem cells from different genetic backgrounds. Thus our system constitutes a powerful tool to generate desired lymphocyte populations both for research and therapy. Future applications of this technology may include treatments for infectious diseases, such as HIV / AIDS, cancer therapy, allergy, and autoimmune disease.

The present invention provides methods of modulating mammalian, particularly human, stem cell and progenitor cell differentiation to regulate and control the differentiation and maturation of these cells along specific cell and tissue lineages. The methods of the invention relate to the use of certain small organic molecules to modulate the differentiation of stem cell populations along specific cell and tissue lineages, particularly embryonic-like stem cells originating from a postpartum placenta or stem cells isolated form sources such as cord blood. The invention also relates to the treatment or prevention of myelodysplastic syndrome or myeloproliferative syndrome, or symptoms thereof, comprising administration of JNK or MKK inhibitors, alone or in combination, as well as with or without the use of unconditioned cells or cells conditioned in accordance with other aspects of the invention. Finally, the invention relates to the use of such differentiated stem cells in transplantation and other medical treatments.

The present invention relates to MHC-peptide complexes and uses thereof in the diagnosis of, treatment of or vaccination against a disease in an individual. More specifically the invention discloses MHC complexes comprising cancer antigenic peptides and uses there of.

The present invention relates to methods of modulating mammalian stem cell and progenitor cell differentiation. The methods of the invention can be employed to regulate and control the differentiation and maturation of mammalian, particularly human stem cells along specific cell and tissue lineages. The methods of the invention relate to the use of certain small organic molecules to modulate the differentiation of stem or progenitor cell populations along specific cell and tissue lineages, and in particular, to the differentiation of embryonic-like stem cells originating from a postpartum placenta or for the differentiation of early progenitor cells to a granulocytic lineage. Finally, the invention relates to the use of such differentiated stem or progenitor cells in transplantation and other medical treatments.

The present invention is directed to the use of immunomodulatory compounds, particularly members of the class of compounds known as IMiDs™, and more specifically the compounds 4-(Amino)-2-(2,6-dioxo(3-piperidyl))-isoindoline-1,3-dione and 3-(4-amino-1-oxo-1,3-dihydroisoindol-2-yl)-piperidine-2,6-dione, to induce the expression of fetal hemoglobin genes, genes essential for erythropoiesis, and genes encoding alpha hemoglobin stabilizing protein, within a population of CD34+ cells. These compounds are used to treat hemoglobinopathies such as sickle cell anemia or β-thalassemia, or anemias caused by disease, surgery, accident, or the introduction or ingestion of toxins, poisons or drugs.

The present invention is directed to universal T cells and their use in treating diseases and other physiological conditions. More specifically, the present invention is directed to universal T cells and their use in treating treating B-lineage acute lymphoblastic leukemia (B-ALL) in particular and malignancy in general. The universal T cells contain (i) nucleic acid encoding a chimeric antigen receptor (CAR) to redirect their antigen specificity and effector function and (ii) nucleic acids encoding shRNA and / or siRNA molecules to down-regulate cell-surface expression of T cell classical HLA class I and / or II genes to avoid recognition by recipient T cells. The universal T cells may also contain a nucleic acid encoding a non-classical HLA gene, such as an HLA E gene to enforce expression of HLA E genes and / or an HLA G gene to enforce expression of HLA G genes, to avoid recognition by recipient NK cells. The universal T cells may further contain a nucleic acid encoding a selection-suicide gene.

The invention is directed to modified T cells, methods of making and using isolated, modified T cells, and methods of using these isolated, modified T cells to address diseases and disorders. In one embodiment, this invention broadly relates to TCR-deficient T cells, isolated populations thereof, and compositions comprising the same. In another embodiment of the invention, these TCR-deficient T cells are designed to express a functional non-TCR receptor. The invention also pertains to methods of making said TCR-deficient T cells, and methods of reducing or ameliorating, or preventing or treating, diseases and disorders using said TCR-deficient T cells, populations thereof, or compositions comprising the same.

Methods and compositions are provided for extending the clinical utility of IFN-α in the treatment of a variety of viral and proliferative disorders. Among other aspects, the invention provides methods which increase the efficacy of IFN-α treatment and reduce IFN-α treatment-related side effects. In addition, methods are provided for supporting the survival and for activating natural interferon producing cells (IPCs) in vitro without exogenous IL-3 or GM-CSF. The invention is based on the discovery that certain CpG and non-CpG ISNAs promote survival and stimulation of IPCs.

The present invention relates to a method for isolating stem / progenitor cells from the amniotic membrane of umbilical cord, wherein the method comprises separating the amniotic membrane from the other components of the umbilical cord in vitro, culturing the amniotic membrane tissue under conditions allowing cell proliferation, and isolating the stem / progenitor cells from the tissue cultures. The isolated stem cell cells can have embryonic stem cell-like properties and can be used for various therapeutic purposes. In one embodiment, the invention relates to the isolation and cultivation of stem cells such as epithelial and / or mesenchymal stem / progenitor cells under conditions allowing the cells to undergo mitotic expansion. Furthermore, the invention is directed to a method for the differentiation of the isolated stem / progenitor cells into epithelial and / or mesenchymal cells.

The present invention provides methods for de-differentiating somatic cells into stem-like cells without generating embryos or fetuses. More specifically, the present invention provides methods for effecting the de-differentiation of somatic cells to cells having stem cell characteristics, in particular pluripotency, by introducing RNA encoding factors inducing the de-differentiation of somatic cells into the somatic cells and culturing the somatic cells allowing the cells to de-differentiate.

The present invention provides compositions and methods for inducing maturation of immature dendritic cells (DC) and for priming those cells for inducing a type 1 immune response. The present invention also provides dendritic cell populations useful for activating and for preparing T cells polarized towards production of type 1 cytokines and / or a type 1 response. Similarly, activated, polarized T cell populations, and methods of making the same are provided.

A bone marrow isolate rich in one or more connective tissue growth components, methods of forming the isolate, and methods of promoting connective tissue growth using the isolate are described. A biological sample comprising bone marrow is centrifuged to separate the sample into fractions including a fraction rich in connective tissue growth components. The fraction rich in connective tissue growth components is then isolated from the separated sample. The isolate can be used directly or combined with a carrier and implanted into a patient at a tissue (e.g., bone) defect site. The biological sample can comprise bone marrow and whole blood. The isolate can be modified (e.g., by transfection with a nucleic acid encoding an osteoinductive polypeptide operably linked to a promoter) prior to application to the tissue defect site. The isolate can be made and applied to the tissue defect site in a single procedure (i.e., intraoperatively).

The present invention relates to hematopoietic stem and progenitor cells of neonatal or fetal blood that are cryopreserved, and the therapeutic uses of such stem and progenitor cells upon thawing. In particular, the present invention relates to the therapeutic use of fetal or neonatal stem cells for hematopoietic (or immune) reconstitution. Hematopoietic reconstitution with the cells of the invention can be valuable in the treatment or prevention of various diseases and disorders such as anemias, malignancies, autoimmune disorders, and various immune dysfunctions and deficiencies. In another embodiment, fetal or neonatal hematopoietic stem and progenitor cells which contain a heterologous gene sequence can be used for hematopoietic reconstitution in gene therapy. In a preferred embodiment of the invention, neonatal or fetal blood cells that have been cryopreserved and thawed can be used for autologous (self) reconstitution.

The invention disclosed herein relates generally to immunotherapy and, more specifically, to therapeutic methods for treating tumors and cancerous tissues by first inducing necrosis or apoptosis (e.g., cryotherapy, chemotherapy, radiation therapy, ultrasound therapy, or a combination thereof applied against at least a portion of the tumor or cancerous tissue), and then delivering one or more se doses of antigen presenting cells (e.g., autologous dendritic cells) intratumourally or proximate to the tumor or cancerous tissue, but only after a selected period of time sufficient for the bioavailablity of liberated cancer-specific antigens (monitored over the selected period of time) resulting from the necrosis or apoptosis to be at or near a maximum value. The present invention provides an alternative strategy to the ex vivo loading of target antigen to antigen presenting cells such as, for example, enriched autologous dendritic cells for purposes of enhancing an immune response.

Methods of obtaining a cell population enriched for tumor-reactive T cells, the method comprising: (a) obtaining a bulk population of T cells from a tumor sample; (b) specifically selecting CD8+ T cells that express any one or more of TIM-3, LAG-3, 4-1BB, and PD-1 from the bulk population; and (c) separating the cells selected in (b) from unselected cells to obtain a cell population enriched for tumor-reactive T cells are disclosed. Related methods of administering a cell population enriched for tumor-reactive T cells to a mammal, methods of obtaining a pharmaceutical composition comprising a cell population enriched for tumor-reactive T cells, and isolated or purified cell populations are also disclosed.

A method of expanding / maintaining undifferentiated hemopoietic stem cells or progenitor cells by obtaining undifferentiated hemopoietic stem cells or progenitor cells; and either seeding the undifferentiated hemopoietic stem cells or progenitor cells into a stationary phase plug-flow bioreactor in which a three-dimensional stromal cell culture has been pre-established on a substrate in the form of a sheet, the substrate including a non-woven fibrous matrix forming a physiologically acceptable three-dimensional network of fibers, thereby expanding / maintaining undifferentiated hemopoietic stem cells or progenitor cells, or culturing the undifferentiated hemopoietic stem cells or progenitor cells in conditioned medium obtained from such a reactor.