266 results about "Interferon" patented technology

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 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.

The invention discloses a method for establishing a hemophagocytic syndrome in-vitro cell disease model, and belongs to the technical field of biology. Based on human PBMC construction, the reaction of a human immune system can be truly reflected, experimental result deviation caused by species difference in an animal model is avoided, and a more accurate model basis is provided for research of human diseases. In addition to T cell over-activation, the HLH model of the present application has a clear key feature of NK cell reduction, which is HLH, accompanied by up-regulation of cytokines such as interferon-gamma and IL-10. The establishment process of the model is rapid and efficient, the experimental period is remarkably shortened, a large number of samples or drugs can be rapidly screened, the research efficiency is improved, and the conversion process from basic research to clinical application is accelerated. The method can be used for researching various mechanisms related to the HLH, is beneficial to more comprehensive understanding of pathogenesis of the HLH, and provides a theoretical basis for developing preliminary screening of targeted drugs.

The invention discloses an engineered exosome for breaking through a pyroptosis immune starting and maintaining barrier as well as a preparation method and application of the engineered exosome. The exosome is constructed by loading an immune checkpoint inhibitor into a pre-stimulated exosome, and the exosome is derived from immune cells, high-expression interferon gamma and granzyme A. The expression of the tumor cell GSDMB is up-regulated by delivering the interferon gamma through the exosome, and the exogenous granzyme A cuts the GSDMB to trigger pyroptosis; meanwhile, an immune checkpoint inhibitor blocks a PD-1 / PD-L1 pathway in situ, T cell depletion is reversed, and release of endogenous granzyme A is promoted; the pyroptosis cells release antigens to activate the T cells, the activated T cells continuously secrete granzyme A / interferon gamma to form a cascade amplification effect, and the problem of double barriers existing in the pyroptosis immune cycle of granzyme A-GSDMB is solved. The engineered exosome can improve the infiltration degree of CD8 + T cells, and is suitable for treating tumors such as liver cancer and non-small cell lung cancer.

The present invention provides methods, compositions, systems, and kits comprising nano-satellite complexes and / or serum albumin carrier complexes, which are used for modulating antigen-specific immune response (e.g., enhancing anti-tumor immunity). In certain embodiments, the nano-satellite complexes comprise: a) a core nanoparticle complex comprising a biocompatible coating surrounding a nanoparticle core; b) at least one satellite particle attached to, or absorbed to, the biocompatible coating; and c) an antigenic component conjugated to, or absorbed to, the at least one satellite particle component. In certain embodiments, the complexes further comprise: d) a type I interferon agonist agent. In some embodiments, the serum albumin complexes comprise: a) at least part of a serum albumin protein, b) an antigenic component conjugated to the carrier protein, and c) a type I interferon agonist agent.

The present invention relates to agents, compositions, and methods for treating or ameliorating symptoms of cancer. Exemplary synergistic therapies include the use of antisense oligonucleotide agents to suppress expression of TGF-β2, alone and in combination with interferon-gamma. One or more biomarkers can be used to select subjects for treatment.

To provide a human interferon-beta mutant having a double mutation and a method for improving the safety of the human interferon-beta mutant.SOLUTION: Provided are a human interferon-beta variant comprising an amino acid sequence in which the 17th amino acid cysteine of human interferon-beta is substituted with serine and the 27th amino acid arginine is substituted with threonine, and a method for improving the stability of a human interferon-beta R27T variant, the method comprising the step of changing the 17th amino acid cysteine of a human interferon-beta R27T variant, in which the 27th amino acid arginine of human interferon-beta is substituted with threonine, to serine.SELECTED DRAWING: Figure 1

The instant disclosure is directed to polymer engineered forms of interferon- gamma (IFN-γ) cysteine mutein compounds, compositions comprising the compounds, and related methods and uses, for example, in the treatment of conditions responsive to therapy with IFN-γ.

A cancer immunotherapy for treating cancers such as melanoma is presented. A method for treating cancer in a subject via administration of anti-LY6E antibody to the subject. The method can further include administering an IFNAR blockade to inhibit type-1 interferon (IFN) signaling, thereby enhancing the ant-tumoral cytotoxic activity of T cells. The IFNAR can include anti-IFNα. The method can also include administering anti-PD1 antibody prior to, commensurate, or after treatment with anti-LY6E. A composition for treating cancer and modulating immune responses in a subject is also included. The composition can include, among other things, the anti-LY6E antibody, the IFNAR blockade, and anti-PD1. The composition and method also present a mechanism to modulate immune response in a subject by preventing upregulation of a Ly6ahigh T-cell subpopulation in response to a stimulus such as cancer, UVB, or interferons.

The present disclosure relates to a novel recombinant influenza virus, in which an interferon-beta gene, which is a foreign gene associated with an antiviral action, is introduced to an NS1 gene which is an influenza virus gene that is expressed first in the host to suppress the host immune system when infected with the influenza virus, and, in contrast to existing research, the interferon-beta is separated from the NS1 protein to carry out an intrinsic function of interferon-beta of inducing an antiviral action.

The invention discloses an application of compounds N-(1-naphthyl)-2-phenoxy acetamide and N-(1-naphthyl)-2-(phenylamino) ethyl thioamide in preparation of cryptosporidium resisting medicines, and belongs to the technical field of medicines and veterinary medicines of anti-parasitic medicines. The compound is obtained through functional group modification by taking NSC158011 as a pilot structure and can efficiently inhibit the activity of cryptosporidium parvum lactic dehydrogenase, and the inhibition rates respectively reach 60-70% and gt; 90%. An in-vitro experiment shows that parasite load is obviously reduced in HCT-8 cells by the two; in vivo, in a gamma-interferon gene knockout mouse and calf infection model, the fecal oocyst load is reduced by 40-100 times, the intestinal barrier repair can be promoted, and the safety is good. The invention reveals that the compound has efficient insect-resistant activity, high safety and intestinal protection effect for the first time, and provides important material basis and technical support for developing a new generation of cryptosporidium-resistant drugs.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APCs.

Provided is a promoter having high activity in an activated T-cell. The promoter comprises, from 5′-end to 3′-end, a CMV enhancer, an IFNγ promoter, and a long terminal repeat sequence from human T-cell leukemia virus that are connected in sequence. The promoter exhibits greater activity in an activated immune cell than the existing promoters and is low in activity or inactive in other non-immune cells.

The present disclosure relates to a BCG based therapeutic agent using a BCG strain that overexpresses the STING agonist, c-di-AMP. This BCG strain, called BCG-disA-OE, enhances the elevated trained immunity of macrophages and promotes early anti-viral Type I interferon responses in a subject, providing protection against viral infections such as primary respiratory infections and SARS-CoV-2 infection.

Provided are a fusion protein, a preparation method therefor and the use thereof. The fusion protein contains a His tag, a SUMO tag, and natural canine interferon-α, wherein the His tag has an amino acid sequence as represented by SEQ ID NO: 11, the SUMO tag has an amino acid sequence as represented by SEQ ID NO: 12, and the natural canine interferon α has an amino acid sequence as represented by SEQ ID NO: 7. The fusion protein exhibits an extremely significant increase in expression level and yield, has preparation stability and biological activity significantly greater than those of a native canine interferon-α protein, and has good safety.

Methods and compositions for treating a corneal wound and / or increasing a population of limbal epithelial stem cells (LESCs) and / or early transit amplifying cells (eTAs) in the limbal epithelium of a subject in need thereof. The methods can include administering a therapeutic agent to the subject that: i) results in an increase in concentration of IFITM1 (Interferon Induced transmembrane Protein 1) in the limbal epithelium of the subject; and / or ii) results in a decrease in concentration of OVOL1 (Ovo Like Zinc Finger 1) in the limbal epithelium of the subject. Also provided are adeno-associated viruses (AAVs). The AAVs comprise a heterologous nucleic acid sequence encoding IFITM1 or a variant thereof, operably linked to a regulatory sequence.

A Toll-like receptor (TLR) is an indispensable component of an innate immune system and plays a key role in identifying and coping with microbial pathogens. TLR7, TLR8, and TLR9 are located in the endosome-lysosome compartment within the cell and then exclusively used to detect nucleic acids of a microorganism after the microorganism is swallowed and reaches the endosome compartment. The biological importance of the TLR agonists lies in that they can be used as powerful tools for studying innate immune responses, developing vaccines and potential therapeutic applications. In addition, TLR agonists have been explored for use as immunotherapy, while these TLR antagonists can be used as new pathogenic nodes in the context of different autoimmune diseases. Therefore, the agonists and antagonists of the endosomal TLR have therapeutic significance in different clinical backgrounds. The previous study on 8-oxo adenines shows that the C-6-site-NH2 group is extremely important for the recognition of agonistic active sites and the subsequent induction of interferon (IFN). The present invention explores the ability of a hydrogen-substituted 8-oxopurine derivative that does not contain an essential C-6 amine group. The C-6 amino group in the 8-oxopurine derivative is substituted by hydrogen (H), providing an exciting opinion for regulating the endosome TLRs (Toll-Like Receptors). The ability of 8-oxopurine derivatives to modulate the endosomal TLR has been reported, which derivatives are related / interrelated to various substitutions at N-7, N-9 and C-2, all derivatives containing hydrogen at C-6. Structure 1

Aspects of the disclosure relate to compositions and methods for modulating the immune response of a subject. The disclosure is based, in part, on compositions comprising a bacterial consortium that promotes interferon (IFN) response in the gut microbiome of a subject and enhances the anti-tumor effects of certain immune checkpoint inhibitor (ICI) therapies. In some embodiments, the compositions are useful for treating a subject having cancer.

Cyclic dinucleotides (CDRs) are signaling molecules for cancer therapy, acting as second messengers for intracellular events initiated by GPCR activation and stimulating factors for the interferon gene (STING), thus significantly influencing tumor suppression. Simultaneously, when cancer occurs in a subject, angiogenesis and cell growth proceed at very high rates in vivo, creating a hypoxic environment due to incomplete angiogenesis in cancerous tissue. This environment can be highly conducive to the proliferation of anaerobic bacteria such as Salmonella strains or Escherichia coli. Therefore, this invention relates to a DNA construct incorporating a gene encoding an enzyme for synthesizing cancer therapeutic signaling molecules (e.g., CDRs), or to strains transformed with a vector containing the DNA construct. According to the invention, the DNA construct or strains transformed with a vector containing the DNA construct target cancer in a subject and then secrete C-di-AMP or C-di-GMP synthases in the surrounding environment of the cancer, thus enabling highly effective prevention or treatment of cancer while allowing for real-time cancer diagnosis.

The invention discloses a bovine I-type tau interferon-ferritin fusion protein as well as a mutant and application thereof. The bovine I-type tau interferon is fused with a ferritin subunit, and interferon molecules are highly repeatedly and orderly displayed on the surface of a ferritin nanocage by utilizing the self-assembly characteristic of ferritin, so that a conformation suitable for the ferritin nanocage to play functions is formed, and the expression level, the structural stability and the antiviral activity of the tau interferon are remarkably improved. The fusion protein is subjected to rational design mutation to obtain a single-site or multi-site mutant with significantly improved antiviral activity and stability. According to the invention, a silkworm or insect cell eukaryotic expression system is adopted to express the fusion protein or the mutant thereof, and the expression system is safe to operate, simple and convenient in procedure, low in cost and extremely beneficial to large-scale industrial production; the prepared fusion protein or mutant nanoparticles can be applied to preparation of a plurality of drugs for preventing or treating bovine viral infection, tumors and immune system diseases and immunologic adjuvants for vaccine compatibility.

The invention is in the field of prevention or treatment of diseases, in particular infectious diseases, and more particularly in the field of multivalent vaccines. The inventors characterized 5′ copy-back DI-RNAs produced by recombinant MV strains, including rMV-based vaccines and wild-type MV (wt-MV). The efficiency of these DI-RNAs productions in different cell types was compared. For the first time 5′ copy-back DI-RNAs specific binding to RIG-I, MDA5 and LGP2 was assessed and linked to functional outcome in type-I IFN signalling. The inventors provide a composition of products comprising at least (i) a mixture of particles of a rescued recombinant MV-derived virus encoding at least one antigen (ii) a recombinant and / or purified protein, comprising at least one antigen. Regardless of the presentation of the products, and in particular regardless of whether the products are separated or readily separable or presented as a mixture.

The invention provides novel modulators of STING (Stimulator of Interferon Genes) and pharmaceutical compositions thereof, as well as methods of their preparation and use, in therapy of various diseases and conditions, such as cancer, infectious and autoimmune diseases or disorders.

Pathogenic infections trigger a complex regulatory system of innate and adaptive immune responses designed to defend against the pathogen in the host organism. One of the many responses to pathogen invasion, e.g., viral, bacterial, fungal or parasitic infection, is the induction of interferon (IFN) production, a pleiotropic group of cytokines that play a critical role in human immune responses by 'interfering' with pathogen activity, e.g., viral replication, among others. Described herein are compositions and methods for inducing Type I interferon production. The compositions described comprise immunostimulatory complexes and RNA duplexes. Compositions comprising the immunostimulatory complexes and RNA duplexes described can be used for the treatment of diseases or disorders that respond to interferons.

A composition and a new method of manufacturing and producing such composition including modified interferon alpha 2 b, modified acetylated interferon alpha 2 b, and / or a mixture thereof is disclosed herein.

The invention discloses a novel benzothiazole compound as well as a preparation method and application thereof. According to the novel benzothiazole compound, through targeted activation of an RIG-I / OAS innate immune pathway, expression of key proteins and genes such as OAS1 and RIG-I can be rapidly up-regulated, secretion of type I interferon and proinflammatory factors is induced, and instant immune enhancement is achieved; more importantly, by performing long-term functional reprogramming on innate immune cells (such as mononuclear cells and dendritic cells), persistent'innate immune memory '(namely immune domestication) can be induced. The dual-action mechanism can significantly enhance the activation of antigen presenting cells and promote the generation and long-term maintenance of memory B cells and effector memory T cells, has no significant toxicity to liver functions, can be used as an immunologic adjuvant and an immunodomestication molecule of an RSV vaccine, can synergistically improve the vaccine-induced RSV specific antibody titer and neutralizing antibody level, and can be used for preparing an immunologic adjuvant for the RSV vaccine. Long-acting immune protection is provided, and a brand new solution is provided for research and development of RSV vaccines.

In certain aspects, provided herein are mutant stimulator of interferon genes (STING) polypeptides, compositions thereof and methods of using the same, wherein the mutation is within the dimerization interface of the STING, and wherein the mutation reduces the ability of the mutant STING polypeptide to mediate protein leakage across a membrane compared to a wild-type STING polypeptide.

Described herein are nucleic acids and recombinant viral vectors comprising the nucleic acids, where the nucleic acids encode a payload of interest (e.g., interferon).

Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) synthase (cGAS) is an enzyme sensor of double-stranded DNA (dsDNA) that serves to trigger activation of the cGAS-stimulator of interferon genes (STING) pathway. The inhibition of cGAS with Cladophorol A is described herein.

The invention provides a supplementary material added in a virus culture process and a use method of the supplementary material. The supplementary material comprises the following components: glucose, GluMAX and soybean lecithin. Supplementary materials are added into the culture medium, so that glycometabolism, lipid metabolism, nucleic acid translation and protein synthesis of host cells can be remarkably enhanced; effect pathways of interferon can be influenced, interferon stimulation gene expression is inhibited, and therefore the cell antiviral effect is inhibited. The cell maintenance can be promoted, and the cell apoptosis after virus infection is delayed. In conclusion, the virus yield can be remarkably improved.