691 results about "Interferon" patented technology

The present invention discloses a human serum albumin-targeting nanobody and its application. A variety of human serum albumin-targeting nanobodies that can be used to construct long-acting fusion protein drugs and their immune screening methods are disclosed. The antibody is composed only of the heavy chain variable region and can be fused and expressed with therapeutic proteins or polypeptide drugs such as interleukin, interferon, and tumor necrosis factor in an Escherichia coli expression system. The fusion protein has the activity of specifically binding to human serum albumin, has a relatively high affinity, can effectively extend the drug half-life, and does not affect the biological activity of the recombinant protein drug at the same time.

The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.

The invention discloses a grass carp gamma interferon fusion protein as well as a mutant, a coding gene and application thereof. In order to improve the expression quantity or expression efficiency of the grass carp gamma interferon, codon optimization and mutation are carried out on the coding gene of the grass carp gamma interferon to obtain the grass carp gamma interferon mutant. The fusion protein is further obtained by connecting the grass carp gamma interferon mutant with the C end of the grass carp ferritin heavy chain subunit of which the last 17 amino acids are removed through a connecting peptide. In order to further improve the antiviral activity of the fusion protein, the obtained fusion protein is subjected to single-point mutation, and the titer of the fusion protein is remarkably improved. The fusion protein is expressed by a silkworm cell eukaryotic expression system, and the fusion protein shows a conformation suitable for the interferon to play functions based on the ferritin self-assembly characteristic, so that the titer of the interferon in a host is effectively improved, and the in-vivo and in-vitro half-life period of the interferon is prolonged. The invention has application prospects in preparation of drugs or reagents for preventing or treating viral diseases of grass carp and the like.

The present invention relates, in part, to chimeric proteins comprising consensus interferon, or a variant thereof, and their use as therapeutic agents.

The invention relates to application of a GATA3 inhibitor and a PD1 inhibitor in preparation of a medicine for treating breast cancer, and belongs to the technical field of biological medicine. The invention discloses application of a GATA3 inhibitor and a PD1 inhibitor in preparation of a medicine for treating breast cancer. The GATA3 regulates the transcription regulation of IFNbeta by inhibiting the enhancer activity of IFNB1, down-regulates an I-type interferon signal channel, inhibits the secretion of an MHC-I antigen presentation channel and a chemotactic factor CCL5 of breast cancer cells, reduces immune recognition, and achieves the purpose of immune escape. The immunotherapy for inhibiting GATA3 combined with the PD1 inhibitor to treat breast cancer effectively treats breast cancer mice, improves the IFN beta level in the mice, promotes the MHC-I antigen presentation pathway of the mice, improves the CCL5 level in the mice, and improves the CD8 + T cell level in a tumor immune microenvironment, thereby reducing tumor occurrence and inhibiting tumor growth.

The invention discloses an immunosensor for detecting cytokine interferon gamma through electrochemiluminescence as well as a preparation method and application of the immunosensor. The immunosensor comprises a three-electrode system consisting of an immunoelectrode, a reference electrode and a counter electrode, the immunoelectrode is a VMSF modified electrode confined to cerium dioxide nano enzyme and platinum nano particles, and is obtained by covalently immobilizing an IFN-gamma antibody and closing a non-specific site; when the immunosensor is used for detection, a solution containing luminol is used as an electrolyte. The CeO2 and the PtNPs which are confined in the nano channel show a remarkable synergistic catalysis effect. Compared with direct modification on a plate electrode, CeO2-PtNPs has higher catalytic activity and stability. The sensor provided by the invention is used for INF-gamma detection, has the advantages of high sensitivity, low detection limit and wide detection range, does not need complex pretreatment and separation processes during detection, reduces the detection cost, is simple to operate, and is suitable for large-scale application.

The invention belongs to the technical field of medicines, and particularly relates to a benzothiophene compound as well as a pharmaceutical composition, a pharmaceutical preparation and application thereof. The benzothiophene compound has a structure as shown in a formula (I), has a very strong excitation effect on an STING-mediated interferon signal channel, can be used as a small-molecule STING agonist, and is used for clinical treatment (especially immunotherapy) of tumors or infectious diseases. # imgabs0 #

The present invention relates to compounds of formula (I) and salts, stereoisomers, tautomers or N-oxides thereof that are useful as modulators of STING (Stimulator of Interferon Genes). The present invention further relates to the compounds of formula (I) for use as a medicament and to a pharmaceutical composition comprising said compounds.

The present invention discloses salts of a Compound 1:useful in the prophylaxis and / or treatment of inflammatory conditions, autoimmune diseases, proliferative diseases, allergy, transplant rejection, diseases involving degradation and / or disruption of cartilage homeostasis, congenital cartilage malformations, and / or diseases associated with hypersecretion of IL6 or interferons.

The invention relates to a cyclopeptide inhibitor aiming at human STING (stimulating interferon gene) and application of the cyclopeptide inhibitor. The cyclic peptide can specifically bind to and inhibit activation of human STING. The invention also provides a nanoparticle delivery system for loading the cyclopeptide on a cationic polymer PBAE and an amphiphilic polymer pDMA-pEPEMA, and a preparation method of the nanoparticle delivery system. The cyclic peptide and the nanoparticles thereof can be used for preparing medicines for treating autoimmune diseases (such as systemic lupus erythematosus and the like) caused by excessive activation of the cGAS-STING signal pathway. Compared with the existing small molecule STING inhibitor, the cyclopeptide inhibitor provided by the invention has higher specificity, stability and inhibition effect.

The invention discloses an effect of an Intestinia butyriproducens bacterium in anti-tumor immunotherapy, and finds that colonization of the Intestinia butyriproducens bacterium in intestinal tracts can inhibit growth of CT26 mouse subcutaneous transplanted tumors with poor response to the tumor immunotherapy, meanwhile, growth of human colorectal cancer cells is remarkably inhibited, and apoptosis of tumor cells is promoted for the first time. The application of the Intestinia butyriproducens bacterium in the anti-tumor immunotherapy has the advantages that the effect of the intestinia butyriproducens bacterium in the anti-tumor immunotherapy is achieved, and the application of the intestinia butyriproducens bacterium in the anti-tumor immunotherapy in the anti-tumor immunotherapy in the anti-tumor immunotherapy in the anti-tumor immunotherapy is achieved. Meanwhile, after colonization of the strain and combined administration of PD-1 monoclonal antibodies, the proportion of CD8 + T cells in mouse tumor infiltration lymphocytes is increased, the proportion of depleted PD-1 + CD8 + T cells is reduced, and the proportion of CD8 + T cells releasing functional cell factors interferon gamma and granzyme B is also increased, which shows that after colonization of the strain, the curative effect of tumor immunotherapy can be enhanced, and the tumor immunotherapy effect can be enhanced. The immunoregulation capability and the great clinical application value are realized.

The present invention discloses an enhanced tumor vaccine adjuvant, and specifically relates to the field of vaccine adjuvants, the adjuvant comprising granulocyte-macrophage colony stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-9 (IL-9), gamma interferon (IFN-γ) and at least one additional immunomodulatory factor, wherein the immunomodulatory factor is selected from tumor-specific antigen WT1, CD40 ligand (CD40L), Toll-like receptor agonist or a combination thereof. The tumor vaccine adjuvant of the present invention can enhance the body's immune response to the tumor vaccine and improve the prevention and treatment effect of the tumor vaccine on tumors.

Methods for interfering or controlling IFN induction, IFN production and / or IFN activity are disclosed, harnessing viral mechanisms for evading or suppressing host anti-viral immune reactions. These methods comprise administration of one or more viral messenger RNAs (mRNAs) coding for proteins or peptides that control or interfere with signal transduction upstream and / or downstream of IFN induction, thereby providing a means for preventing or treating diseases, disorders or conditions associated with increased IFN production, such as cancer, autoimmune diseases, inflammatory diseases and interferonopathies.

The invention relates to a recombinant expression cat interferon-omega gene and a preparation method and application thereof, the nucleotide sequence of the cat interferon-omega gene is as shown in SEQ ID NO.1, and the cat interferon-omega gene is obtained by introducing an Fc fusion fragment to the C terminal and / or N terminal of the natural gene sequence of the cat interferon-omega. XTEN or PAS is introduced to prolong a peptide fragment, and original glycosylation modification sites on a natural sequence are reserved. The method comprises the following steps: cloning a cat interferon-omega gene into an expression vector containing double promoters, further transfecting into a cell, carrying out stable cloning and screening, establishing a high-expression cell strain, and carrying out fermentation culture in a bioreactor. According to the invention, the cat interferon-omega gene is subjected to multiple modification and is efficiently expressed in a CHO-K1GS system, so that the protein yield, the stability and the half-life period are remarkably improved; the obtained fusion protein is high in purity and strong in activity, can obviously enhance immune response and protection effect when being matched with cat vaccines, and is good in safety.

The present disclosure provides antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4 (and optionally cynomolgus monkey, mouse, and / or rat B7-H4) and compositions comprising such antibodies or antigen-binding fragments thereof. In a specific aspect, the antibodies or antigen-binding fragments thereof that specifically bind to human B7-H4 increase T cell proliferation, increase interferon-gamma production, and / or deplete B7-H4 expressing cells via ADCC activity. The present disclosure also provides methods for treating disorders, such as cancer, by administering an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4.

The invention discloses a nanoparticle for targeted protein degradation and a degradation method. The nanoparticles can enhance uptake of cells and effectively encapsulate specific antibodies for recognizing target proteins, and meanwhile, the interferon component can induce expression of TRIM family proteins in the cells. After ingestion into the cell, the antibody released by the nanoparticle can bind to the target protein and bind to the TRIM family protein to mediate degradation of the target protein. In this process, although the TRIM family protein is continuously consumed, the TRIM family protein can be compensated by the TRIM family protein expression induced by the particle of the invention, thereby maintaining efficient degradation.

The present disclosure relates to compositions and methods relating to interferon agonists and their engineered polypeptides. The engineered polypeptides have specificity to receptors in immune systems mediated by Type I interferon (IFN). The present disclosure also relates to methods and system for identifying surrogate agonists for cell surface receptors including dimeric and trimeric receptors.

The invention discloses a targeted human serum albumin nano antibody and application thereof. The invention discloses a plurality of targeted human serum albumin nano antibodies capable of being used for constructing long-acting fusion protein drugs and an immune screening method thereof. The antibody is only composed of a heavy chain variable region and can be subjected to fusion expression with interleukin, interferon, tumor necrosis factors and other therapeutic proteins or polypeptide drugs in an escherichia coli expression system, the fusion protein has the activity of specific binding with human serum albumin, the affinity is high, the half-life period of the drugs can be effectively prolonged, and the anti-tumor effect is good. Meanwhile, the biological activity of the recombinant protein medicine is not influenced.

The invention relates to the field of biological medicine and aquatic products, and discloses a grass carp IFNf interferon and truncated protein and application thereof in virus resistance or bacterium resistance. The applicant discovers the new subtype IFNf of the grass carp interferon for the first time, the protein coded by the new gene has an efficient antiviral effect, and the derived peptide AMP-G2 of the grass carp interferon has broad-spectrum antibacterial activity. The sensitivity of the grass carp interferon IFNf to grass carp reovirus (GCRV) infection is higher than that of other interferon, and the grass carp interferon IFNf shows obvious antiviral activity on the cellular level and can be used for preparing antiviral drugs. The interferon-derived peptide provided by the invention is a host natural peptide, is small in molecular weight and simple to synthesize, has a remarkable bactericidal effect on various bacteria and fungi, and can be used for preparing broad-spectrum antibacterial agents or antibacterial drugs.

The invention belongs to the technical field of biological medicine, and provides CKS1B serving as an immunotherapy response prediction biomarker and application of the CKS1B, and according to the application, CKS1B serves as an immunotherapy response marker, and a CKS1B inhibitor is combined with an active component to treat a model mouse. In-vitro cell experiments are adopted to evaluate the immunotherapy prediction effect of the CKS1B as a biomarker on esophageal squamous carcinoma, a Cks1b overexpression tumor mouse model, a homologous mouse model and a human immune reconstruction mouse model are established, and a CKS1B inhibitor is combined with active ingredients to treat the two models; results show that the CKS1B inhibitor combined with the active component can promote removal of esophageal squamous carcinoma cells by CD8 + T cells, inhibit interferon signal channels and antigen presentation, effectively recover immune response, inhibit tumor cell proliferation and significantly reduce tumor volume, so as to achieve the purpose of treating esophageal squamous carcinoma.

Provided are a fusion protein comprising recombinant porcine interferon λ1 and a use thereof, and a preparation method and use for the fusion protein. The fusion protein is formed by respectively linking porcine interferon λ1 to other fragments (such as porcine interferon γ) and / or porcine serum albumin (PSA) directly or indirectly by means of linker elements. The porcine interferon λ1 fusion protein can be prepared by using a mammalian cell expression system on the basis of genetic engineering technology. Compared with natural porcine interferon λ1, the provided recombinant porcine interferon λ1 fusion protein has a long half-life period and can be used for preparing drugs for preventing or treating porcine viral diseases.

The invention belongs to the technical field of veterinary medicine, and provides a co-expressed recombinant porcine alpha and gamma interferon. The I-type interferon alpha and the II-type interferon gamma not only exert the anti-virus, anti-cell division and immune regulation effects of the interferon, but also can activate T cells and natural killer cells, and fully exert the multiple activities of the interferon. The two interferons are co-expressed in insect cells, the expression protein can be folded and then processed and modified, the structure of the expression protein is closer to a natural structure, the biological activity is high, the recombinant protein is easy to purify, the production scale is easy to expand, and live viruses or potential dangerous pathogens do not need to be treated, so that the production cost is reduced; by optimizing the production process and fermentation conditions, the quality and stability of the recombinant protein can be further improved.

An Interferon Gamma Inducible Protein 16 (IFI16) mutant gene and its use as a marker for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease is described. As a result of performing genomic analysis on NAFLD and NASH patient groups, it was confirmed that the frequency of IFI16 single-nucleotide variants (SNVs) including rs2276404, rs73021847, rs7532207, and rs6940 was increased, and the expression of the IFI16 mutant gene was increased depending on the disease stage of liver disease. The IFI16 SNV was highly expressed in infiltrating macrophages, playing a role in macrophage-induced inflammatory processes, and the IFI16 variant bound more strongly to dsDNA than wild-type IFI16, exacerbating the impaired mitochondrial DNA-sensing response signaling of the IFI16-PYCARD-CASP1 pathway. Thus, the IFI16 mutant gene may be used for predicting, diagnosing, or prognosticating risk or severity of chronic liver disease.

The present disclosure provides methods, pharmaceutical compositions, and kits for treating cancer in patients in need thereof. The methods comprise administering to a patient in need a STING (stimulator of interferon genes) agonist, such as Compound No. 14, or a pharmaceutically acceptable salt thereof, in combination with one or more checkpoint inhibitors. Suitable checkpoint inhibitors include anti-PD-1 antibodies, anti-PD-L1 antibodies and anti-CTLA-4 antibodies. Also provided are medicaments for use in treating cancer. Compound No. 14 has the structure:

The invention provides a bovine interferon alpha recombinant protein with a long half-life period, a variant protein and an application of the bovine interferon alpha recombinant protein and the variant protein in virus resistance, a key part with an antiviral effect of BoIFN alpha and a key part with a low toxicity effect of BoIFN tau are connected by using a flexible linker to construct a low-toxicity long-acting interferon, and specific amino acid of the low-toxicity long-acting interferon is subjected to site-specific mutagenesis on the basis of the low-toxicity long-acting interferon; the toxicity and the half-life period are further improved. Tests prove that the long-acting recombinant bovine interferon product prepared by the invention is an efficient, long-acting and broad-spectrum antiviral drug product, has a longer half-life period and higher biological activity than common natural bovine interferon or hybrid interferon, prolongs the half-life period, improves the biological activity, reduces the preparation cost of an interferon preparation, and is suitable for industrial production. The compound has huge potential and value of being developed into broad-spectrum antiviral drugs and veterinary clinical application.

Provided is a Hunner-type interstitial cystitis therapeutic agent that can selectively inhibit IFN-γ without risk of biological contamination and can be stored at room temperature. Provided is a Hunner-type interstitial cystitis therapeutic agent or a reagent for test and research, comprising as an active ingredient a DNA oligonucleotide having a nucleotide sequence set forth in any of SEQ ID NO:1 to 3 and selectively binding to IFN-γ. A base, X, in the sequence of the DNA oligonucleotide having the nucleotide sequence set forth in SEQ ID NO: 3 is an artificially produced base, and the artificially produced base may be chemically modified with a low-molecular-weight compound, a medium-molecular-weight compound, a high-molecular-weight compound, a biopolymer, or a biocompatible polymer.

Provided are cytokine fusion proteins comprising a first cytokine fused to a second cytokine, for example, interleukin-2 (IL-2) or interferon-β (IFN-β) fused to the N-terminus of tumor necrosis factor-α (TNF-α), and related compositions and methods of use thereof for treating cancers, either as standalone agents or in combination with autologous tumor vaccines and / or immune checkpoint modulatory agents.

Provided herein are method for identifying a subject as having or at risk of having myocarditis and / or myositis based on the detection of the level of cytotoxic CD8+ T-cells and / or inflammatory myeloid cells, and / or on the detection of the level of expression of a TNF signaling via NFκB, an interferon-α signaling, an interferon-γ signaling, an IL2 / STAT5 signaling, a hypoxia signaling and / or a complement signaling in CD45+ immune cells. The identification of such patients is used in methods of treating a subject having or at risk of having myocarditis and / or myositis, methods of treating cancer, and methods of treating immune checkpoint therapy (ICT)-related myocarditis and / or ICT-related myositis. The methods of treatment include the administration of a therapeutic compound to inhibit IL-1β and TNF.

The use of formononetin (FMN) in reducing imiquimod (IMQ)-induced inflammatory cytokine expression by means of inhibiting an interferon (IFN) signaling pathway. The FMN can be used for the prevention and treatment of inflammatory skin diseases and the reduction of disease recurrence in the future. Using animal experiments combined with transcriptomics, it is found that the action of FMN on an IMQ-induced mouse model significantly improves inflammatory skin lesion symptoms, and inhibits pathological phenotypes such as the PASI score and epidermal hyperplasia in mice.