86 results about "Interleukin 15" patented technology

The present invention relates to a composition for expanding lymphocytes comprising at least two types of cytokines selected from interleukin 2 (IL-2), interleukin 15 (IL-15) and interleukin 21 (IL-21). It further relates to a Method of preparing a population of clinically relevant lymphocytes, comprising the steps of: obtaining a body sample from a mammal in particular a tissue sample or body liquid sample, comprising at least one lymphocyte and optionally separating the cells in the body sample, culturing the body sample in-vitro to expand and / or stimulate lymphocytes in the sample wherein the culturing comprises using IL-2, IL-15 and / or IL-21, and optionally determining the presence of clinically relevant lymphocyte in the cultured sample. The present invention also relates to an immunotherapy and the population of clinically relevant lymphocytes.

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.

The present invention relates to Fc-IL-15 hybrids, which may or may not include peptide linkers between the IL-15 and the Fc portion, for methods of treatment of tumors and viral infections. The IL-15 hybrids can be Fc-IL-15 or IL-15-Fc hybrids. The Fc-IL-15 hybrids include variants, including the IL-15 and Fc variants. The hybrids preferably (but not necessarily) include peptide linkers between the IL-15 and the Fc portion. These linkers are preferably composed of a T cell inert sequence, or any non-immunogenic sequence.

The present invention relates to the use of interleukin-15 (IL-15) as selectable marker for gene transfer, preferably of at least one gene of therapeutic interest, into a mammalian cell or cell line, in particular a human cell or cell line. The present invention furthermore relates to transgenic mammalian cells or cell lines expressing IL-15 as selectable marker and co-expressing at least one protein of interest encoded by at least one gene of interest, which is preferably a protein of therapeutic interest. The present invention is in particular suitable for chimeric antigen receptors (CARs) as the gene or protein of interest and their expression in lymphocytes. The transgenic mammalian cells and cell lines are furthermore suitable for use as a medicament, in particular in the treatment of cancer and in immunotherapy, such as adoptive, target-cell specific immunotherapy.

A human interleukin 15-Fc fusion protein composed of interleukin 15 and the Fc fragment of human immunoglobulin, which are linked via joining peptide, the nucleic acid ofr coding it, the expression carrier containing said nucleic acid, its composite medicine for preventing and treating microbial infection and its preparing process are disclosed.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and / or survival of NK cells.

Disclosure herein are mutant IL-15 polypeptides and methods for using these polypeptides to modulate the immune response in a patient.

An interleukin-15 (IL-15) gene modified natural killing cell strain for immunotherapy of tumor is prepared through inserting the cDNA coding region of IL-15 in pcDNA3 eucaryotic expression carrier, configuring secretion-type recombinant eucaryotic expression carrier pc DNA3 / IL-15, using liposom to transfecte cell NK-92, adding Geneticin (G418) to screening culture medium, screening, limited dilution to cloned cells, detecting activity, choosing positive cell clones, and amplification.

The invention relates to a PEG interleukin 15 conjugate, namely PEG interleukin 15. PEG and interleukin 15 are connected on an N terminal amino group through or not through small peptide connexon to obtain the uniform PEG interleukin 15 conjugate. The activity of the original interleukin 15 can be at least reserved in vivo, and the PEG interleukin 15 conjugate has longer half-life period and average time to peak.

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 and / 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-15Rα antibodies, fragments of these antibodies, e.g. the Fab or F(ab′)2 fragment, soluble IL-15Rα, fusion proteins consisting of soluble IL-15Rα, and Fc fragment, compounds, e.g. peptides, binding and / or inhibiting functional IL-15 receptor, IL-15 antisense oligonucleotides.

A human interleukin 15-Fc fusion protein composed of interleukin 15 and the Fc fragment of human immunoglobulin, which are linked via joining peptide, the nucleic acid ofr coding it, the expression carrier containing said nucleic acid, its composite medicine for preventing and treating microbial infection and its preparing process are disclosed.

The invention relates to a culture medium efficiently amplifying autologous NK cells and a culture method. The culture medium internally contains interleukin 2(IL-2), interleukin 15(IL-15), interleukin 7(IL-7), interleukin 12(IL-12), tumor necrosis factor alpha (TNFalpha) and CD3-antibody, can efficiently amplify and activate NK cells so as to obtain a large quantity of highly active immune cells with majority of NK cells to be transferred back to human bodies, and has remarkable curative effect in anti-tumor, anti-virus infection and immune adjustment related diseases. The culture medium efficiently amplifying autologous NK cells comprises the culture medium for cultivating cells and added factors added into the culture medium for cultivating cells, is used for cultivating and amplifying a large quantity of autologous activated NK cells, and is characterized in that the added factor comprises interleukin 2(IL-2), interleukin 15(IL-15), interleukin 7(IL-7), interleukin 12(IL-12), tumor necrosis factor alpha (TNF alpha) and CD3-antibody.

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.

The present invention relates to the use of interleukin-15 (IL-15) as selectable marker for gene transfer, preferably of at least one gene of therapeutic interest, into a mammalian cell or cell line, in particular a human cell or cell line. The present invention furthermore relates to transgenic mammalian cells or cell lines expressing IL-15 as selectable marker and co-expressing at least one protein of interest encoded by at least one gene of interest, which is preferably a protein of therapeutic interest. The present invention is in particular suitable for chimeric antigen receptors (CARs) as the gene or protein of interest and their expression in lymphocytes. The transgenic mammalian cells and cell lines are furthermore suitable for use as a medicament, in particular in the treatment of cancer and in immunotherapy, such as adoptive, target-cell specific immunotherapy.

The invention relates to a drug and a tumor whole-cell vaccine for treating or preventing tumor, and preparation methods and applications of the drug and the whole-cell vaccine, and belongs to the fields of bioengineering and biological immunology. The invention provides a drug with good effect for treating or preventing tumor and a tumor whole-cell vaccine. The drug comprises the tumor whole-cell vaccine, a cation liposome, and recombinant plasmid for encoding interleukin-15 gene. The drug has the dual actions of tumor prevention immunization and anti-tumor immune treatment, and has durable action and obvious tumor prevention or treatment effect.

The present invention relates to methods and compositions for monitoring, diagnosis, prognosis, and determination of treatment regimens in subjects suffering from or suspected of having a renal injury. In particular, the invention relates to using assays that detect one or more markers selected from the group consisting of Cytoplasmic aspartate aminotransferase, soluble Tumor necrosis factor receptor superfamily member 5, soluble CD40 Ligand, soluble C-X-C Motif chemokine 16, S100-A12, Eotaxin, soluble E-selectin, Fibronectin, Granulocyte colony-stimulating factor, Granulocyte-macrophage colony-stimulating factor, Heparin-binding growth factor 2, soluble Hepatocyte growth factor receptor, Interleukin-1 receptor antagonist, Interleukin-1 beta, Interleukin-10, Interleukin-15, Interleukin-3, Myeloperoxidase, Nidogen-1, soluble Oxidized low-density lipoprotein receptor 1, Pappalysin-1, soluble P-selectin glycoprotein ligand 1, Antileukoproteinase, soluble Kit ligand, Tissue inhibitor of metalloproteinase 1, Tissue inhibitor of metalloproteinase 2, soluble Tumor necrosis factor, soluble Vascular cell adhesion molecule 1, and Vascular endothelial growth factor A as diagnostic and prognostic biomarkers in renal injuries.

The present invention relates to a composition for expanding lymphocytes comprising at least two types of cytokines selected from interleukin 2 (IL-2), interleukin 15 (IL-15) and interleukin 21 (IL-21). It further relates to a Method of preparing a population of clinically relevant lymphocytes, comprising the steps of: obtaining a body sample from a mammal in particular a tissue sample or body liquid sample, comprising at least one lymphocyte and optionally separating the cells in the body sample, culturing the body sample in-vitroto expand and / or stimulate lymphocytes in the sample wherein the culturing comprises using IL-2, IL-15 and / or IL-21, and optionally determining the presence of clinically relevant lymphocyte in the cultured sample.The present invention also relates to an immunotherapy and the population of clinically relevant lymphocytes.

The present invention provides, in certain aspects, a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15), and methods for producing such cells. The invention further provides methods of using a natural killer (NK) cell that expresses all or a functional portion of interleukin-15 (IL-15) to treat cancer in a subject or to enhance expansion and / or survival of NK cells.

The γc-family cytokines, Interleukin-2 (IL-2), Interleukin-4 (IL-4), Interleukin-7 (IL-7), Interleukin-9 (IL-9), Interleukin-15 (IL-15), and Interleukin-21 (IL-21), are associated with important human diseases, such as leukemia, autoimmune diseases, collagen diseases, diabetes mellitus, skin diseases, degenerative neuronal diseases and graft-versus-host disease (GvHD). Thus, inhibitors of γc-cytokine activity are valuable therapeutic and cosmetic agents as well as research tools. The present embodiments relate to the design of peptide antagonists based on the consensus γc-subunit binding site to inhibit γc-cytokine activity. In several embodiments, peptide antagonists exhibit Simul-Block activity, inhibiting the activity of multiple γc-cytokine family members.

The present invention provides a method for in-vitro culturing and expanding natural killer (NK) cells in a cell culture medium comprising a population of NK cells, the method comprising a) adding an effective concentration of interleukin-21 (IL-21) at the beginning of the culturing process to said medium, b) adding repeatedly an effective concentration of interleukin-2 (IL-2) and / or interleukin-15 (IL-15) to said medium, and c) adding repeatedly feeder cells or membrane particles thereof to said medium, wherein said feeder cells are B cell derived which are EBV immortalized; and wherein said expansion of NK cells in said cell culture medium is maintained for at least 3 weeks.

This invention relates to the expansion of non-haematopoietic tissue-resident γδ T cells in vitro by culturing lymphocytes obtained from non-haematopoietic tissue of humans or non-human animals in the presence of interleukin-2 (IL-2) and / or interleukin-15 (IL-15) and the absence of TCR activation or co-stimulation signals, without any direct contact with stromal or epithelial cells. Methods of non-haematopoietic tissue-resident γδ T cell expansion are provided, as well as populations of non-haematopoietic tissue-resident γδ T cells and uses thereof.

The present invention relates to a process for purifying an interleukin-15 / Fc fusion protein from a composition, which process comprises a) applying the composition to an affinity chromatography column and eluting a first IL-15 / Fc eluate from the column and b) applying the eluate of step a) to an ion exchange chromatography column and eluting a second IL-15 / Fc eluate from the column; and to a purified interleukin-15 / Fc fusion protein and a composition, in particular a pharmaceutical composition, comprising such a fusion protein.

The invention relates to a fusion protein prodrug taking interleukin 15 as an active ingredient. The prodrug is a fusion protein and includes the following structural units: (1) a first structural unit is the fragment of one or a subunit of an interleukin 15 (IL15) acceptor; (2) a second structural unit is IL15 having activity; (3) a third structural unit located on the C end of the fusion proteinis an antibody Fc fragment; (4) a connection fragment 1 is used for connecting the first, second and third structural units; (5) a fourth structural unit located on the N end of the fusion protein isthe extracellular fragment of the beta subunit of the IL15 acceptor; and (6) a connection fragment 2 is used for connecting the fourth structural unit and residual structural units.

The present invention concerns methods of treating a disease such as leukemia in a subject by administering natural killer (NK) cells. In particular aspects, HLA-C1-licensed KIR2DL2 / 3 and KIR2DS2 NK cells are administered to a subject with an HLA-C genotype either homozygous or heterozygous for the C1 allele, or HLA-C2 licensed cells are administered to a subject with an HLA-C genotype homozygous for the C2 allele. In further aspects, the NK cells are genetically modified to express a chimeric antigen receptor and interleukin 15.

The invention relates to a composition comprising regulatory T (Treg) cells or effector T cells (Teff) which stably express an interleukin selected from the group consisting of interleukin-2 (IL-2) or interleukin-15 (IL-15).

The invention relates to a genetically modified cell of coexpression mouse membranous type interleukin 15 and retinoic acid early transcript 1 epsilon (Rae-1 epsilon) and a preparation method thereof. The genetically modified cell is a BaF3 cell which can stabilize the genetically modified cell of the coexpression membranous type IL-15 and Rae-1 epsilon protein. The genetically modified cell can be prepared by a method comprising the following steps: amplifying a mouse Rae-1 epsilon gene and a mouse membrane expression type IL-15 gene by a polymerase chain reaction (PCR) technology; respectively inserting the amplified mouse Rae-1 epsilon gene and the amplified mouse membrane expression type IL-15 gene into two polyclone sites of an eukaryotic expression vector pVITRO2-mcs to acquire a recombined vector; transfecting the recombined vector into a mouse tumor cell strain BaF3; and acquiring the genetically modified cell by antibiotics screening and flow cytometry sorting. The genetically modified cell can provide IFN-gamma producing killer dendritic cells (IKDC) with triple stimulating signals as an instrument for efficiently amplifying and activating the IKDC in vitro. In addition, the genetically modified cell can also be used for antineoplastic immunotherapy research.

The invention provides a tumor targeting fusion protein at least comprising (i) an IL-15 polypeptide, an IL-15 polypeptide variant, or a functional fragment thereof, (ii) an IL-15Ra polypeptide, an IL-15Ra polypeptide variant, or a functional fragment thereof, (iii) an Fc structural domain, an Fc variant, or a functional fragment thereof, and (iv) an RGD polypeptide or a variant thereof. The arraying sequence of the components of the fusion protein is preferably the RGD polypeptide-the Fc structural domain-the IL-15 polypeptide-the IL-15Ra polypeptide. On one hand, the tumor targeting fusion protein can enhance the anti-tumor efficacy of the IL-15, and on the other hand, the tumor targeting fusion protein overcomes the problem of short half-life of the IL-15, also can target to a tumor site, and targetedly acts on tumor cells. In addition, the tumor targeting protein can be efficiently expressed and purified, also has efficient antitumor activity, and has the potential to become an anti-tumor therapeutic drug.

The invention discloses a human Vgamma9Vdelta2T cell proliferation method and a culture medium. Interleukin-15 and vitamin C are added in the proliferation culture process of human Vgamma9Vdelta2T cells, compared with a traditional proliferation method, the method can improve the proliferation efficiency and purity of the human Vgamma9Vdelta2T cells, and the cultured human Vgamma9Vdelta2T cells which have higher anti-apoptosis capacity and longer cell survival time at the same time have higher anti-apoptosis capacity, longer cell survival time and higher expression level of key killing molecules NKG2D and thus have high killing capacity for tumor cells.