423 results about "Interleukin" patented technology

The present disclosure provides drug responsive domains derived from human carbonic anhydrase 2 that can modulate protein stability for human interleukin 15 (IL15) payloads, as well as compositions and methods of use thereof.

Provided are methods for treating cancer using local administration of certain CpG oligonucleotides (CpG ODN) and systemic administration of a checkpoint inhibitor such as an anti-PD-1 antibody, an anti-PD-L1 antibody, and / or an anti-CTLA-4 antibody. In preferred embodiments, the CpG ODN are selected based on their propensity to induce high amounts of interferon alpha (IFN-α) and T-cell activation relative to interleukin-10 (IL-10) and B-cell activation. In certain embodiments, the methods further include pretreatment with radiotherapy, to potentiate the combination immunotherapy.

Disclosed are a new interleukin-2 (IL-2) mutant protein and the use thereof. Compared with wild-type IL-2, the IL-2 mutant protein has improved properties, such as an improved IL-2 receptor binding property and improved druggability. Also provided are a fusion protein, dimer and immunoconjugate comprising the IL-2 mutant protein, nucleic acids encoding the IL-2 mutant protein, the dimer and the immunoconjugate, and a vector and host cell comprising the nucleic acid. Further provided are methods for preparing the IL-2 mutant protein, the fusion protein, the dimer and the immunoconjugate, a pharmaceutical composition containing same, and the therapeutic use thereof.

This invention discloses a combination of biomarkers for the auxiliary diagnosis of chronic pain comorbid with depression and its application, belonging to the fields of in vitro diagnostics (IVD) and clinical testing technology. The biomarker combination includes interleukin-6 (IL-6), interleukin-12 (IL-12), and the concentration ratio of kynurenic acid to 3-hydroxykynurenine (KYNA / 3-HK). This invention also discloses the application of this biomarker combination in an in vitro diagnostic kit for chronic pain comorbid with depression. Experimental results show that the diagnostic efficacy of this biomarker combination (AUC=0.871) is significantly better than that of a single biomarker, effectively distinguishing patients with chronic pain comorbid with depression from those without chronic pain, providing an objective auxiliary diagnostic tool for clinical practice.

Provided is a bispecific antibody and use thereof, the bispecific antibody comprising: a first domain that specifically binds the interleukin-6 receptor IL-6R, and a second domain that specifically binds interleukin-23. The bispecific antibody can simultaneously target IL-6R and IL-23p19, with stronger specificity, more accurately targeting tumor cells and reducing the adverse effects of off-target toxicity and can perform a unique function to play a biological function that is difficult to achieve with monoclonal antibody drugs. Compared with monoclonal antibody combination therapies, it can also effectively reduce the cost of treatment and break the current upper limit of therapeutic efficacy in the treatment of autoimmune diseases such as rheumatoid arthritis and IBD.

The technology described herein is directed to methods of generating CD4+CD8- single-positive T cells from CD4+CD8+ double positive T progenitor cells using differentiation in the presence of interleukin-7 (IL-7) and an anti-CD3 agent and in absence of Notch ligand and an anti-CD28 agent. Also described herein are CD4+CD8- single-positive T cells made by the methods described herein, which can be used for therapeutic applications.

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

This disclosure provides an antibody (or antigen-binding protein) comprising at least one, preferably two, antigen-binding domains that bind to the human IL-6 receptor, wherein the antibody inhibits IL-6 transsignaling via the human soluble IL-6 receptor while maintaining IL-6 classical signaling via the human membrane-bound IL-6 receptor, and the antibody is capable of binding to both the human soluble IL-6 receptor and the human membrane-bound IL-6 receptor. Compositions comprising the antibody or antigen-binding protein are also provided, along with encoding nucleic acid molecules and expression vectors.

The present invention generally relates to immunoconjugates, particularly immunoconjugates comprising a mutant interleukin-2 polypeptide and an antibody that binds to PD-1. In addition, the invention relates to polynucleotide molecules encoding the immunoconjugates, and vectors and host cells comprising such polynucleotide molecules. The invention further relates to methods for producing the mutant immunoconjugates, pharmaceutical compositions comprising the same, and uses thereof.

The present application discloses an IL-2 derivative, by introducing at least one cysteine residue on the basis of wild type IL-2, partially or completely closing the binding plane of the IL-2 derivative with the alpha receptor subunit, while basically retaining the affinity to the beta and gamma receptor subunit complex.

The invention discloses a biomarker combination related to hypoxia-induced neuroinflammation and application of the biomarker combination, and belongs to the technical field of biomarker detection. The marker combination disclosed by the invention consists of serum S100 beta protein, neuron-specific enolase, interleukin-6, high-mobility group protein B1 and neurofilament light-chain protein. The marker combination can be used for stratification of nervous system injury risk of severe hypoxia patients and acquisition of prognosis evaluation data. According to the detection method disclosed by the invention, synchronous quantitative detection of five markers is realized by adopting a multiple immunofluorescent microsphere technology, and a marker combination scoring algorithm is established to comprehensively evaluate the severity of the hypoxia-related neuroinflammation.

The disclosure provides for various methods including a method of reducing the severity of bispecific T cell engager (BiTE) or chimeric antigen receptor T cell (CAR-T) induced cytokine release syndrome (CRS) comprising administering to a patient in need thereof an amount of a composition comprising an interleukin 10 (IL-10) or an IL-10 agent, an interleukin 4 (IL-4) or an IL-4 agent, or combinations thereof.

The invention relates to recombinant IL2 variant polypeptides suitable to generate IL2 prodrugs and the prodrugs comprising said variant polypeptides that may be activated at a target site.

This invention discloses a fusion protein targeting the urokinase-type plasminogen activator receptor and its application in the field of anti-aging. The fusion protein is composed of a hepatocyte growth factor active domain and a humanized anti-uPAR single-domain antibody linked by a flexible linker peptide, and its specific amino acid sequence is SEQ ID NO:3. This fusion protein can specifically bind to uPAR, which is highly expressed on the surface of senescent cells, with intramolar affinity, achieving targeted delivery of the hepatocyte growth factor active domain. In vitro experiments have demonstrated that this protein can significantly reverse the aging phenotype of human fibroblasts, effectively reduce aging-related β-galactosidase activity, p16INK4a protein expression, and interleukin-6 secretion, and promote cell proliferation. In a rapidly aging mouse model, this protein can systematically improve age-related physiological functional decline. The fusion protein of this invention achieves specific targeting and efficient treatment of senescent cells, providing a new solution for the development of anti-aging drugs.

The invention discloses an application of Northeast tiger interleukin-15 in preparation of an antiviral drug. According to the invention, IL-2 family genes (IL-2, IL-4, IL-9, IL-15 and IL-21) and IL-13 genes of the northeast tiger are cloned and successfully expressed. Functional experiments show that all cytokines can promote lymphocyte proliferation, F81 cells are pretreated with IL-15 and then exposed to feline panleucopenia virus (FPV) derived from northeast tiger, and different exposure time is set for subsequent experimental research. The consistency of flow cytometry, protein expression analysis and ROS staining results shows that IL-15 can significantly weaken oxidative stress and apoptosis induced by FPV infection. In conclusion, the molecular and functional characteristics of the northeast tiger IL-2 cell factor family are clarified, and IL-15 is highlighted as a cell factor with a potential antiviral protection effect. The results provide technical means for cytokine-based immunological research and potential treatment strategy development to support health and protection of northeast tigers in the future.

The application discloses an electrochemical sensor for detecting IBD protein markers and a preparation method thereof. The electrochemical sensor is composed of a CNT-embedded semi-cured PDMS flexible substrate, deposited gold nanoparticles and a nucleic acid sensing layer. The nucleic acid sensing layer comprises a tumor necrosis factor-alpha sensor, an interleukin 6 sensor, an interleukin 8 sensor, a transforming growth factor beta 1 sensor, a reference electrode and a counter electrode. The tumor necrosis factor-alpha sensor, the interleukin 6 sensor, the interleukin 8 sensor and the transforming growth factor beta 1 sensor all adopt single-stranded aptamers modified by a signal molecule methylene blue, and the nucleotide sequences corresponding to the single-stranded aptamers are SEQ ID NO. 1-4. The application can improve the modulus matching of the sensor and human tissue and excellent biocompatibility, realize accurate detection of low-concentration biomarkers and stable signal output of the sensor under a strain working condition.

Cannabidiol, or a pharmaceutically acceptable prodrug, derivative, salt, or solvate thereof, for use in treating or preventing recurrent pericarditis is disclosed. The effectiveness of cannabidiol in attenuating the levels of interleukin-1β (IL-1β) and IL-6, and the transcription of pro-IL-1β and NLRP3 mRNA in in vitro models are disclosed. Also disclosed are experiments showing cannabidiol to be effective in preventing an increase in the pericardial space (which is an indicator of pericardial effusion) and the pericardial thickness in an in vivo mouse model of pericarditis.

The invention relates to the technical field of electrochemical luminescence sensing, and discloses an electrochemical luminescence immunosensor for detecting interleukin-1 beta, a preparation method and application thereof, the electrochemical luminescence immunosensor comprises a working electrode, a reference electrode and a counter electrode; the working electrode comprises a substrate electrode and an ordered mesoporous silica film (SNF) modified on the surface of the substrate electrode; a composite nano-enzyme containing cobaltosic oxide nanoparticles and nitrogen-doped graphene quantum dots is loaded in a nano-pore channel of the SNF, the outer surface of the SNF is modified with an epoxy group, and an anti-interleukin-1beta antibody is covalently immobilized through the epoxy group; a detection system of the electrochemical luminescence immunosensor is a luminol / dissolved oxygen system. According to the electrochemical luminescence immunosensor, a luminol / dissolved oxygen system signal can be remarkably enhanced, and high-sensitivity and accurate quantitative detection of interleukin-1 beta is realized under a neutral condition.

Disclosed herein are branched chain amino acid transaminase 1 (BCAT1) inhibitors and uses thereof. More specifically, disclosed are BCAT1 inhibitors that limit amino acid metabolism essential for CD4+ T-cell responses and their use in preventing, improving, or treating inflammatory disease or autoimmune disease. By identifying that BCAT1 acts as a major regulator in the inflammatory response of CD4+ T-cells, it is possible to regulate the inflammatory response by CD4+ T cells secreting interleukin-17 (IL-17), which is a major immune cell of autoimmune diseases, by utilizing a BCAT1 inhibitor.

Described herein are antibodies, or antigen binding fragments thereof, that bind thymic stromal lymphopoietin (TSLP) and interleukin (IL)-13 in combination and methods of use thereof. In certain aspects, described herein are methods of inhibiting TSLP and IL-13 biological activity. In certain aspects, described herein are pharmaceutical compositions comprising the anti-TSLP and anti-IL-13 antibodies, or antigen binding fragments thereof. In certain aspects, the antibodies and methods described herein are used for treatment of an inflammatory disease or disorder associated with elevated levels of TSLP and / or IL-13.

The invention discloses a nucleotide for inhibiting expression of ILKAP (Interleukin-7-Kinase Associated Protein) related circular RNA (Ribonucleic Acid) and application of the nucleotide, and the nucleotide is characterized in that the nucleotide sequence is CGUCAGUACUCGGGUUUCA, and the expression level of hsacirc0001116 can be specifically and obviously reduced. Experimental results prove that the nucleic acid molecule can effectively interfere with the expression of hsacirc0001116 in human non-small cell lung cancer A549 cells, and can significantly inhibit the survival of lung cancer cells. In addition, when the nucleic acid molecule is combined with an existing antitumor drug for use, a synergistic treatment effect can be generated.

Activatable interleukin 12 (IL12) fusion proteins and constructs are disclosed herein that contain at least one of the following structures: N'-DD-L1-MM-L2-IL12-C', C'-DD-L1-MM-L2-IL12-N', N'-DD-L1-IL12-L2-MM-C', C'-DD-L1-IL12-L2-MM-N', wherein L1 is a first linker or is absent; L2 is a second linker; DD is a dimerization domain; MM is a masking moiety; IL12 comprises an IL12α (p35) domain and an IL12β (p40) domain; N' is an amino terminus of the activatable IL12 fusion protein; and C' is a carboxy terminus of the activatable IL12 fusion protein, wherein at least one of L1 and L2 comprises a cleavable moiety (CM); or a first IL12 subunit and a second IL12 subunit; at least one of a first linking region (LR1) and a second linking region (LR2); and a half-life extending moiety (EM), wherein at least one of the LR1 and the LR2 comprises a cleavable moiety (CM); or dimers thereof.

Provided are a novel peptide inhibitor of the interleukin-23 receptor, a stereoisomer or a pharmaceutically acceptable salt or solvate thereof, or a pharmaceutical composition containing the same, and the use of the peptide inhibitor in the treatment or prevention of diseases or conditions including inflammatory bowel disease, Crohn's disease and psoriasis.

The present invention relates to a novel interleukin-2 (IL-2) mutant protein. The present invention further provides a fusion protein and an immunoconjugate comprising the IL-2 mutant protein, a nucleic acid encoding the IL-2 mutant protein, and a vector and a host cell comprising the nucleic acid. The present invention further provides a method for preparing the IL-2 mutant protein, a pharmaceutical composition comprising the IL-2 mutant protein, and therapeutic use of the mutant protein.

The fully human monoclonal antibody comprises (i) an antigen-binding variable region that exhibits very high binding affinity for IL-1α, and (ii) a constant region that is effective both in binding C1q but activating the complement system, and in binding to multiple different Fc receptors.

The present invention relates to the identification of novel therapeutic targets and their use in the mitigation of inflammatory pathologies. In particular, the present invention concerns the field of anti-interleukin-17A antibodies, pharmaceutical compositions comprising said antibodies and medical uses of the same. Further aspects of the invention relate to a polynucleotide encoding the anti-interleukin-17A, vectors comprising the polynucleotide and host cells incorporating said vectors. In a further aspect the invention describes a peptide for the identification of anti-interleukin-17 compounds.

The present invention relates, in part, to chimeric proteins and Fc-based chimeric protein complexes comprising IL-6 or modified IL-6 and their use as therapeutic agents. The present invention further relates to methods of treatment of various diseases, such as cancer.

Provided herein are engineered proteins and methods of treatment using the engineered proteins wherein the engineered proteins comprise a first region and a second region wherein the first region binds to TREM1, a variant thereof, or a functional fragment thereof, and wherein the second region binds to interleukin, such as TREM1, a variant thereof, or a functional fragment thereof. Wherein the interleukin comprises a protein selected from any one of the IL-1 family, the IL-6 family, the IL-12 family and the IL-23 family, a variant thereof, or a functional fragment thereof.