40 results about "IL-2 receptor" patented technology

A crystalline composition comprising a crystal of the IL-6 receptor I chain is provided. Also provided are methods of using the crystal and related structural information to screen for and design compounds that interact with IL-6R, or variants thereof. Also provided arc methods of modulating an IL-6 receptor comprising contacting the IL-6 receptor with a compound identified by the screening method of the invention.

The present inventors investigated the antitumor effects of anti-IL-6 receptor antibodies against prostate cancer. The result showed that the anti-IL-6 receptor antibodies had both in vivo and in vitro antitumor effects against prostate cancer. It was also revealed that the hPM1 antitumor effect is via IL-6 receptor.

The present invention generally relates to mutant interleukin-2 polypeptides that exhibit reduced affinity to the α-subunit of the IL-2 receptor, for use as immunotherapeutic agents. In addition, the invention relates to immunoconjugates comprising said mutant IL-2 polypeptides, polynucleotide molecules encoding the mutant IL-2 polypeptides or immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant IL-2 polypeptides or immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

The present inventors discovered that neural invasion is suppressed by inhibiting IL-6 in a model for neural invasion of pancreatic cancer, and completed the present invention. The present inventors also demonstrated that: an IL-6 receptor is expressed in cells of human pancreatic cancer cell lines; and IL-6 enhances the chemotactic and migratory activities and intracellular signaling of pancreatic cancer cells; and thus pancreatic cancer can be treated by inhibiting IL-6. Furthermore, the present inventors found that neural invasion of human pancreatic cancer can be suppressed, from the results of administering IL-6 inhibitors to neural invasion model mice.

The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions. The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.

The present invention provides a mesothelioma therapeutic agent containing an interleukin-6 (IL-6) antagonist such as antibody to IL-6 receptor (IL-6R), and a mesothelioma cell growth inhibitor containing an IL-6 antagonist such as antibody to IL-6R.

The present invention provides pharmaceutical compositions comprising second-generation molecules that are superior than TOCILIZUMAB, by altering the amino acid sequences of the variable and constant regions of TOCILIZUMAB, which is a humanized anti-IL-6 receptor IgG1 antibody, to enhance the antigen-neutralizing ability and increase the pharmacokinetics, so that the therapeutic effect is exerted with a less frequency of administration, and the immunogenicity, safety and physicochemical properties (stability and homogeneity) are improved. The present invention also provides methods for producing these pharmaceutical compositions.The present inventors have successfully generated second-generation molecules that are superior to TOCILIZUMAB by appropriately combining amino acid sequence alterations in the CDR domains, variable regions, and constant regions.

A method for the treatment or prevention of autoimmune diseases, allergic or atopic disorders, and graft rejection is provided, comprising inducing the death by apoptosis of a subpopulation of T lymphocytes that is capable of causing such diseases, while leaving substantially unaffected the majority of other T lymphocytes. Cell death is achieved by cycle(s) comprising challenging via immunization these T cells with antigenic substance at short time intervals, or by immunization followed by administering interleukin-2 (IL-2) when these T cells are expressing high levels of IL-2 receptor so as to cause these T cells to undergo apoptosis upon re-immunization with the antigenic peptide or protein. These methods are applicable to the treatment of autoimmune diseases such as, for example, multiple sclerosis, uveitis, arthritis, Type I insulin-dependent diabetes, Hashimoto's thyroiditis, Grave's thyroiditis, autoimmune myocarditis, etc., allergic disorders such as hay fever, extrinsic asthma, or insect bite and sting allergies, food and drug allergies, as well as for the treatment or prevention of graft rejection.

This invention is directed to a stable liquid pharmaceutical formulation comprising a high concentration, e.g. 50 mg / ml or more, of antibody in about 20-60 mM succinate buffer or 30-70 mM histidine buffer, having pH from about pH 5.5 to about pH 6.5, about 0.01-0.1% polysorbate, and a tonicity modifier that contributes to the isotonicity of the formulation. This liquid formulation is stable at refrigerated temperature (2-8° C.) for at least 1 year, and preferably 2 years. This liquid formulation is suitable for subcutaneous injection. The preferred antibodies include Daclizumab, a humanized anti-IL-2 receptor monoclonal antibody; HAIL-12, a humanized anti-IL-12 monoclonal antibody; HuEP5C7, a humanized anti-L selectin monoclonal antibody; and Flintozumab, a humanized anti-gamma interferon monoclonal antibody.

Disclosed herein are novel compounds with activity at RARβ 2 receptors. Further disclosed are the use of such compounds for treatment of or to alleviate symptoms of cancer, neurological disorders such as memory deficits and schizophrenia, neurodegenerative disorders such as Parkinson's and Alzheimer's diseases, inflammatory disorders such as psoriasis and rheumatoid arthritis, eye disorders and depression.

A pharmaceutical combination comprising an accelerated lymphocyte homing agent in free form or in pharmaceutically acceptable salt form, and one or more compounds selected from the group consisting of an antibody to the IL-2 receptor, an immunosuppressive macrocyclic lactone and a soluble human complement inhibitor is used to treat or prevent insulin-producing cell graft rejection.

The present invention provides methods for inhibiting or attenuating tumor growth in a subject by administering an IL-6 antagonist to the subject. In certain embodiments, the methods of the invention are used to inhibit the growth of an anti-VEGF-resistant tumor in a subject. The IL-6 antagonist may be, e.g., an antibody that specifically binds IL-6R. The IL-6 antagonist may be administered in combination with a VEGF antagonist, and / or an EGFR antagonist.

The invention discloses a method for breeding IL-12p40 (- / -) IL-2R alpha (- / -) mice used as novel hepatic fibrosis and primary biliary cirrhosis animal models. The method includes steps of (1), performing cross breeding on IL-2R alpha (+ / -) mice and IL-12p40(- / -) mice to obtain IL-12p40(+ / -) IL-2R alpha (+ / -) mice by means of breeding; (2), performing cross breeding on IL-12p40(- / -) mice and the IL-12p40(+ / -) IL-2R alpha (+ / -) mice obtained in the step (1) to obtain IL-12p40(- / -) IL-2R alpha (+ / -) mice by means of breeding; (3), performing inbreeding on the IL-12p40(- / -) IL-2R alpha (+ / -) mice obtained in the step (2) and obtaining the identified IL-12p40(- / -) IL-2R alpha (- / -) mice. The method has the advantages that IL-12p40 is an important cell factor in the immune system of a patient, and functions and differentiation of CD4+T and CD8+T cells can be affected by the IL-12p40; IL-2R alpha is an alpha chain of an IL-2 receptor and plays a key role in keeping the balance of the immune system of the patient.

The invention relates to an electrochemical biologic receptor sensor taking a recombination EGFP-beta 2-AR cell membrane as a biosensor identification element and an application thereof in the detection of a beta 2-excitant. The electrochemical receptor biosensor comprises a working electrode, a counter electrode and a reference electrode. The electrochemical receptor biosensor is characterized inthat the working electrode adopts a gold electrode modified by the recombination EGFP-beta 2-AR cell membrane; the counter electrode adopts a platinum wire electrode; and the reference electrode adopts a saturated calomel electrode. The expression system established by the invention is successful, establishes a firm technical foundation for a beta 2 receptor-matcher detection system and also strongly prompts that the combination of the beta 2 receptor-matcher detection system and the electrochemical biosensor provides feasibility for searching and establishing the quick, sensitive and broad-spectrum detection of the beta 2-excitant.

The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize a CLLD8 protein as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.

The invention relates to a recombinant immune cytokine targeting PD-L1 and IL-2 receptors and an application of the recombinant immune cytokine. By means of a whole-genome synthesis technology, an Fcheavy-chain gene of an IgG1 subclass antibody of a PD-L1 monoclonal antibody is fused with a mutated IL-2 gene through linker, and the novel recombinant immune cytokine is obtained. The recombinant immune cytokine has better tumor-inhibiting activity, especially for tumor types with PD-L1 weak expression, and achieves effects of activating in-vivo lymphocytes and promoting cytokine production.

The receptor for Interleukin 35 (IL-35) is provided. The Interleukin 35 Receptor (IL-35R) comprises a heterodimeric complex of the Interluekin12Rβ2 receptor and the gp130 receptor. Various compositions comprising the IL-35R complex, along with polynucleotides encoding the same and kits and methods for the detection of the same the same are provided. Methods of modulating the activity of IL-35R or modulating effector T cell functions are also provided. Such methods employ various IL-35R antagonists and agonists that modulate the activity of the IL-35R complex and, in some embodiments, modulate effector T cell function. Further provided are methods for screening for IL-35R binding agents and for IL-35R modulating agents. Various methods of treatment are further provided.

The invention provides a compound of a formula (I) shown in the specification with selective beta1-adrenergic inhibitory activity, and the chemical name of the compound is clerodane-3,12E-di-double bond-15,16-dioctyl phthalate. The compound of the formula (1) has selective beta1-adrenergic receptor inhibitory activity, the inhibitory activity of the compound upon a beta1 receptor is 6 times or greater of that upon a beta2 receptor, cardiovascular diseases such as hypertension, myocardial ischemia, cardiomegaly, coronary heart diseases, myocardial infarction, stroke, atherosclerosis, cardiac failure and angina pectoris can be effectively treated, and in addition, side effects of a non-selective beta1-adrenergic receptor inhibitor can be avoided. The invention further relates to a pharmaceutically acceptable salt of the compound of the formula (I), a medicine composition and a preparation with the compound of the formula (I) and / or the pharmaceutically acceptable salt thereof, and application of the compounds and compositions in preparing medicines for treating cardiovascular diseases.

It is found that neuroinvasion in a neuroinvasion model for pancreatic cancer can be inhibited by inhibiting IL-6. Further, it is demonstrated that an IL-6 receptor is expressed in a human pancreatic cancer cell line and IL-6 can increase the chemotactic ability, the migratory ability and the intercellular signaling of a pancreatic cancer cell, and it is found that pancreatic cancer can be treated by inhibiting IL-6. Still further, it is found that human pancreatic cancer neuroinvasion can be inhibited by administering an IL-6 inhibitor to a mouse neuroinvasion model.

Methods and compositions for preventing an immune response to an immunogenic therapeutic agent [i.e. anti-drug antibody (ADA), a.k.a. anti-therapeutic antibody (ATA)] are disclosed. One of the disclosed methods comprises administering an effective amount of an immunosuppressant such as an IL-2 signaling pathway inhibitor, including an antagonist, super agonist or partial agonist to the cytokine IL-2, to the IL-2 receptor (IL-2R), or to IL-2R signal transduction molecules. Inhibitors can be in the form of antibodies or antibody fragments, peptide inhibitors, fusion molecule, small molecules, antibody / small molecule conjugates. Administration of a given inhibitor can decrease the incidence and / or magnitude of an immune response or prevent an immune response, including an antibody response, to a potentially immunogenic therapeutic agent in a non-human primate (NHP). Some of the disclosed methods produce a tolerizing effect in NHPs.

The invention relates to 7-zminocephalosporanic acid derivative, Cefazolin, for use as the inhibitor of IL-15 and IL-2 receptors in the prevention and treatment of IL-15 and IL-2 overproduction related diseases.

Regulation of expression of CTL activity by macrophage migration inhibitory factor (MIF) is disclosed. In a mouse model using the EL4 tumor, cultured splenocytes from tumor-primed mice secrete high levels of MIF following antigen stimulation in vitro. Parallel splenocytes treated with neutralizing anti-MIF mAb showed a significant increase in CTL response against tumor cells compared to control mAb-treated cultures, with elevated expression of IFN gamma . Histology of tumors from anti-MIF treated animals showed increases in infiltration of both CD4<+> and CD8<+> T cells, as well as apoptotic tumor cells, consistent with observed augmentation of CTL activity in vivo by anti-MIF, which was associated with enhanced expression of the common gamma c chain of the IL-2 receptor that mediates CD8<+>T cell survival. CD8<+> cells of anti-MIF treated tumor-bearing mice showed increased migration into tumors of control mice. Methods for enhancing a CTL response by inhibition of MIF are disclosed.

Compositions comprising nucleic acids encoding the α chain of IL-2 receptor (IL-2Ra, CD25), homologs and fragment thereof, are effective in the treatment and prevention of T cell mediated pathologies. Methods are provided for enhancing anti-ergotypic T cell activity in a subject in need thereof, and for treating or preventing T cell mediated pathologies, such as autoimmune disease, inflammatory diseases and graft rejection.

The invention relates to a method to build a recipient cell model of neuronal nicotinic type acetylcholine subtype of the technical field. The method comprises the following steps: (1) gene APP695 is cloned into plasmid pcDNA3.1 (-); (2) pcDNA3.1(-)-APP695 is stably transferred into SH-EP1-Alpha4 Beta2 cell through a liposome method and is screened by adding pressure and by screening antibiotics; (3) expression of APP695 mRNA cloned by sable transfection cell is identified; (4) expression of APP695 and ABetaprotein cloned by stable transfection cell is identified; (5) receptor function of upper nicotineAlpha4 Beta2 cloned by the stable transferction cell is identified; patch-clamp is used in the process of receptor function identification of upper nicotine cloned by stable transfection cell. The stable expression nicotineAlphaBeta2 recipient and A Beta cell line are obtained in the invention, and central neuronal nicotinic acetylcholine Alpha4 Beta2 subtype recipient and cell models of A Beta co-expression are built, and the invention provides a powerful tool for solving the problems of AD incidence and focusing problem about nicotinic recipients subtype, providing an effective channel for AD prevention and treatment medicine.

The present provides compounds capable of modulating IL-4 receptor-mediated IgE production, as well as IL-4 induced processes associated therewith, methods and kits for identifying such compounds that utilize an adenosine kinase as a surrogate analyte and methods of using the compounds in a variety of in vitro, in vitro and ex vivo contexts.