55 results about "B-cell proliferation" patented technology

Compounds of Formula I

and all pharmaceutically acceptable forms thereof, are described herein.

The variables R₁, R₂, R₃, Z₂, and Q, shown in Formula I are defined herein.

Pharmaceutical compositions containing one or more compounds of Formula I, or a pharmaceutically acceptable form of such compounds, and one or more pharmaceutically acceptable carriers, excipients, or diluents are provided herein.

Methods of treating patients suffering from certain diseases responsive to inhibition of tyrosine kinase activity are also given. In certain embodiments the diseases are responsive to inhibition of Btk activity and/or B-cell proliferation. Such methods comprise administering to such patients an amount of a compound of Formula I effective to reduce signs or symptoms of the disease. These diseases include cancer, an autoimmune and/or inflammatory disease, or an acute inflammatory reaction. Thus methods of treatment include administering a sufficient amount of a compound or salt as provided herein to decrease the symptoms or slow the progression of these diseases.

Other embodiments include methods of treating other animals, including livestock and domesticated companion animals, suffering from a disease responsive to inhibition of kinase activity.

Methods of treatment include administering a compound of Formula I as a single active agent or administering a compound of Formula I in combination with one or more other therapeutic agent.

A method for determining the presence of Btk in a sample, comprising contacting the sample with a compound or form thereof of Formula I under conditions that permit detection of Btk activity, detecting a level of Btk activity in the sample, and therefrom determining the presence or absence of Btk in the sample.

Nucleic acid sequences containing unmethylated CpG dinucleotides that modulate an immune response including stimulating a Th1 pattern of immune activation, cytokine production, NK lytic activity, and B cell proliferation are disclosed. The sequences are also useful as a synthetic adjuvant.

Compositions and methods for modulating the growth, proliferation, and/or differentiation of B-cells in the germinal center are disclosed, and include use of IL-15 inhibitors, antagonists, and agonists. The compositions and methods find use in treating B-cell-related disorders, including neoplasms of the B-cell lineage.

[Object]

A novel and excellent method for preventing or treating rejection in the transplantation of various organs, allergy diseases, autoimmune diseases, hematologic tumor, or the like, based on a PI3Kδ-selective inhibitory action and/or an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action (including an activation inhibitory action), is provided

[Means for Solution]

It was found that a 3-substituted triazine or 3-substituted pyrimidine derivative exhibits a PI3Kδ-selective inhibitory action, and/or an IL-2 production inhibitory action, and/or a B cell proliferation inhibitory action (including an activation inhibitory action), and can be an agent for preventing or treating rejection in the transplantation of various organs, allergy diseases (asthma, atopic dermatitis, etc.), autoimmune diseases (rheumatoid arthritis, psoriasis, ulcerative colitis, Crohn's disease, systemic lupus erythematosus, etc.), hematologic tumor (leukemia etc.), or the like, thereby completing the present invention.

The invention features a method of treating a B-cell proliferative disorder by administering to a patient a BAR agonist, e.g., formulated for administration by a route other than inhalation (such as for oral or intravenous administration), in an amount effective to treat the B-cell proliferative disorder. The BAR agonist may be administered as a monotherapy or in combination with one or more other agents, e.g., a PDE inhibitor, an A2A receptor agonist, or an antiproliferative compound, in amounts that together are effective to treat the B-cell proliferative disorder. The invention further features pharmaceutical compositions and kits including a BAR agonist, alone or in combination with additional agents, for the treatment of a B-cell proliferative disorder.

Discussed herein are pharmaceutical compositions containing Ibrutinib and processes for preparing them. The compositions may be utilized in the treatment of a variety of conditions including, without limitation, B-cell proliferative disorders such as non-Hodgkin lymphoma (diffuse large B cell lymphoma, follicular lymphoma, mantle cell lymphoma or burkitt lymphoma), Waldenstrom macroglobulinemia, plasma cell myeloma, chronic lymphocytic leukemia, lymphoma, or leukemia. These compositions are designed for oral ingestion. The compositions are contained within a capsule such as a standard or sprinkle or in a liquid formulation such as a suspension. In one embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, and magnesium stearate. In another embodiment, the pharmaceutical composition contains Ibrutinib, a salt, prodrug, or metabolite thereof, microcrystalline cellulose, carboxymethylcellulose sodium, hydroxypropylmethylcellulose, citric acid monohydrate, disodium hydrogen phosphate, sucralose, sodium methyl parahydroxybenzoate, sodium ethyl parahydroxybenzoate, concentrated hydrochloric acid, sodium hydroxide, and water.

We teach a strategy to obtain large quantities of desired APCs, activated B cells, which are superior in their capacity to present tumor protein antigen in a multiadministration protocol. Human B cells can be obtained from peripheral blood in large numbers. These cells can be activated in vitro by coculture with CD40L (CD40-B cells) and an immunosuppressive agent such as cyclosporin A. They can expanded up to 1x103 to 1x104 fold in 2 weeks or 1x105 to 1x106 fold in 2 months. We demonstrate these cells are most efficient APCs comparable to DCs in stimulating allogeneic CD4+ CD45RA+, CD4+ CD45RO+, and CD8+ T cells. In contrast to DCs, CD40-B cells are fully functional even in the presence of immunosuppressive cytokines such as IL-10 and TGFbeta.

The invention features compositions and methods employing combinations of an A2A receptor agonist and a PDE inhibitor for the treatment of a B-cell proliferative disorder, e.g., multiple myeloma.

The present invention provides novel therapeutic uses for interleukin-1 receptor antagonists for conditions related to interleukin-18, interleukin-12 and interferon-.gamma.. The present invention also provides novel methods for modulating B cell proliferation.

The invention provides divaricate velvetplant root and rhizome polysaccharide and application thereof in preparing a medicine and functional food for immune adjustment and tumor resistance. According to the invention, the prepared divaricate velvetplant root and rhizome polysaccharide can promote mononuclear macrophage strain to phagocytose neutral red and release nitric oxide, can promote B cell proliferation and T cell proliferation, can also obviously improve immunosuppressive mouse spleen and thymus indexes, can improve the transformation and the proliferation of T cells and B cells, can increase the level of immunosuppressive mouse white blood cells, can obviously restrain the growth of tumor tissues, can protect organisms, can restrain the decline of weight, can gain weight, and can obviously restrain the migration of epidermic cells in veins. In addition, polysaccharide is the main functional component of divaricate velvetplant roots and rhizomes, has various health-care efficacies, is derived from purely natural materials, does not have any side effects, and can be developed into medicines and health-care products for immune adjustment, tumor resistance and angiogenesis resistance, so that the divaricate velvetplant root and rhizome polysaccharide has favorable market application prospects.

The invention discloses a nanometer antibody for resisting a B cell growth stimulating factor and a use thereof and belongs to the field of biotechnology. The nanometer antibody for resisting a B cell growth stimulating factor has an amino acid sequence shown in the formula of SEQ ID NO. 1 in the sequence table. Through screening of multiple nanometer antibodies with high activity and a latent neutralising capacity, the nanometer antibody 52 for resisting BAFF is obtained. The nanometer antibody can specifically bond with a human BAFF antigen, adjust biological activity of the BAFF antigen and related ligands, and effectively inhibit bonding of the BAFF antigen and its acceptors and production of corresponding signal cascade effects. The nanometer antibody for resisting BAFF can block combination of BAFF and its three related receptors, can substantially inhibit B cell proliferation or viability and can be used for detection and /or treatment on a plurality of BAFF expression abnormity-related diseases.

The invention discloses Bcl11a siRNA-585 for inhibiting B-cell lymphoma/leukemia 11A (BCL11A) expression and tumorous B cell proliferation. The sequence of the sense strand of the Bcl11a siRNA-585 is 5'-GAAUCUACUUAGAAAGCGATT-3'; and the sequence of the antisense strand of the Bcl11a siRNA-585 is 5'-UCGCUUUCUAAGUAGAUUCTT-3'. The Bcl11a siRNA-585 can efficiently inhibit BCL11A expression, effectively inhibit tumorous B cell proliferation and promote tumorous B cell apoptosis. The invention also proves that the tumorous B cell proliferation is inhibited more effectively and the tumorous B cell apoptosis is promoted by combining the Bcl11a siRNA-585 and Bc1-2 siRNA. The Bcl11a siRNA-585 for inhibiting the BCL11A expression and the tumorous B cell proliferation has significance for developing new anti-B cell tumor gene medicaments and improving the treatment effect of B cell tumors.

The invention realtes to CD4+T cell derived exosomes and application thereof, and belongs to the field of cytobiology, molecular biology and clinical application. The invention particularly discloses CD4+T cell derived exosomes (named as CD4+ T exo) and application thereof in preparation an adjuvant for enhancing a vaccine immunity effect. It discovers that CD4+ T exo can effectively promote proliferation and activation of B cells in vitro, and can promote the B cells to produce more antibodies. Meanwhile, CD4+ T exo can serve as an adjuvant to enhance the immune effect of sheep red blood cell (SRBC) immunized mice in vivo, can also have obvious enhancing effect on hepatitis B vaccine immunized Babl/c mice, and promotes peripheral blood to produce more hepatitis B surface antibodies (HbsAb). The application of the CD4+T cell derived exosomes can be used for preparing a novel adjuvant for enhancing the antigen/vaccine immunization effect.

The invention relates to recombinant lactic acid bacteria of pig interleukin 10. Ribose nucleic acid (RNA) in pig spleen cells is used as a template; poIL-10 genes are obtained by reverse transcription-polymerase chain reaction (RT-PCR) technology; the poIL-10 genes are transformed into escherichia coli after being connected with a pMD18T vector of a cloning vector; and the poIL-10 genes are inserted into an escherichia coli-lactic acid bacterium shuttle expression plasmid pW425et to build a recombinant plasmid pW425et-poIL-10 and electrically transform the recombinant plasmid pW425et-poIL-10into the lactic acid bacteria to obtain the recombinant lactic acid bacteria capable of stably expressing the pig interleukin 10. The recombinant lactic acid bacteria can be planted in intestinal canals through oral administration, stably express the pig interleukin 10, effectively regulate immune functions of organisms, stimulate proliferation of cells B, improve the levels of IgG, IgM and IgA of serum, improve the capability of the organisms generating specific antibodies for pathogenic microorganisms, ensure healthy growth of pigs and promote sustainable and healthy development of animal husbandry.

Methods for inhibiting proliferation of a B-cell population are provided comprising administering a combination of agents, comprising: (i) at least one P13K-delta selective inhibitor; (ii) at least one anti-CD20 antibody; and (iii) at least one Bruton's tyrosine kinase (BTK) inhibitor. Methods for treating B-cell proliferative disorders, such as B-cell hematological malignancies, as well as kits for carrying out the claimed methods, are also provided.

The invention discloses a nanometer antibody for resisting a B cell growth stimulating factor and a use thereof and belongs to the field of biotechnology. The nanometer antibody for resisting a B cell growth stimulating factor has an amino acid sequence shown in the formula of SEQ ID NO. 1 in the sequence table. Through screening of multiple nanometer antibodies with high activity and a latent neutralising capacity, the nanometer antibody G3 for resisting BAFF is obtained. The nanometer antibody can specifically bond with a human BAFF antigen, adjust biological activity of the BAFF antigen and related ligands, and effectively inhibit bonding of the BAFF antigen and its receptors and production of corresponding signal cascade effects. The nanometer antibody for resisting BAFF can block combination of BAFF and its three receptors, can substantially inhibit B cell proliferation or viability and can be used for detection and /or treatment on a plurality of BAFF expression abnormity-related diseases.

The invention confirms the suppression effect of paclitaxel liposome on B cell proliferation and immunologic function, and the application of paclitaxel liposome on rat CIA treatment.

The invention relates to a culture medium for promoting hybridoma growth and a preparation method thereof. The culture medium for promoting hybridoma growth comprises a 1640 complete medium and recombinant human IL-21 added into the 1640 complete medium, and the concentration of recombinant human IL-21 in the medium for promoting hybridoma growth is 100 ng/mL. According to the above culture medium, the recombinant human IL-21 is added on the basis of a prepared RPMI 1640 complete medium, and the final concentration of recombinant human IL-21 in the culture medium is controlled at 100 ng/mL, so that the growth of hybridoma cells is promoted by promoting B cell proliferation, and also secretion of needed monoclonal antibody by the hybridoma cells is promoted by promoting B cell to secrete specific antibody.

The present invention relates generally to a method of modulating cellular functioning. More particularly, the present invention relates to a method of modulating B cell functioning, for example B cell proliferation, utilising an IDO-mediated tryptophan metabolite as herein defined (particular examples of such IDO-mediated tryptophan metabolites include 3-hydroxykynurenic acid, 3-hydroxyanthranilic acid, picolinic acid, quinolinic acid and tranilast). The method of the present invention is useful, inter alia, in the treatment and/or prophylaxis of conditions characterised by aberrant, unwanted or otherwise inappropriate B cell functioning such as antibody production, autoimmune conditions and B cell proliferation and neoplasias. In a related aspect, the present invention is directed to a method of therapeutically and/or prophylactically treating rheumatoid arthritis via the administration of the above-mentioned compounds.