356 results about "Immunomodulating Agent" patented technology

Provided herein are methods of treating cancer in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a combination of an immunomodulator inhibitor and a compound of Formula (II).

The present disclosure is directed to compounds of Formula (I):which modulate PD-1 / PD-L1 protein / protein interaction, compositions, and methods of treating various diseases, including infectious diseases and cancer.

Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

The invention relates to an active oxygen responsive triptolide prodrug immunoregulation hydrogel preparation as well as a preparation method and application thereof. Triptolide is coupled with an active oxygen responsive group to synthesize a triptolide derivative; then, the triptolide derivative is coupled with polypeptide, and a polypeptide-reactive oxygen responsive group-triptolide conjugate is obtained; then dissolving the polypeptide-active oxygen responsive group-triptolide conjugate in a solvent, standing, and carrying out self-assembly to obtain a triptolide prodrug nanofiber solution; finally, an immunomodulator is added into the triptolide prodrug nanofiber solution for incubation, and the active oxygen responsive triptolide prodrug immunoregulation hydrogel preparation is obtained. The hydrogel preparation disclosed by the invention can responsively release the medicine triptolide and the immunomodulator at the focus part of rheumatoid arthritis, so that the medicine accumulation of non-target organs is reduced, the safety and effectiveness of treatment are improved, and the progress of diseases is effectively controlled.

The invention provides an AS01 derivative adjuvant, a preparation method thereof and application of the AS01 derivative adjuvant in preparation of vaccines or anti-tumor drugs, and belongs to the technical field of biological drugs or products. The AS01 derivative adjuvant is prepared from the following components in parts by mass: 0.5 to 1.0 part of cholesterol, 2.0 to 4.0 parts of dioleoyl lecithin and at least one of the following components in parts by mass: 0.1 to 0.2 part of monophosphoryl lipid A, 0.1 to 0.2 part of QS-21, 0.36 to 0.72 part of 3M-052, 0.4 to 0.8 part of muramyl dipeptide and 0.2 to 0.4 part of oligodeoxynucleotide. According to the AS01 derived adjuvant, a novel synergistic adjuvant system is developed by integrating various immunomodulators, so that the immunogenicity of a vaccine is enhanced. The HPV vaccine is prepared on the basis of the AS01 derived adjuvant, so that the immunogenicity can be enhanced, and good anti-tumor activity can be achieved. Therefore, the invention provides a new strategy for immunotherapy of HPV-related tumors.

Drug delivery nanoparticle compositions and methods for the treatment of a cancer are provided that can be used individually or in combination. These compositions and methods include: (1) exogenous vaccination using neoantigens or tumor-associated antigens to potentiate an anti-tumor immune response; (2) nanoparticle-based drug delivery targeting the liver, aimed at reprogramming the hepatic immune environment to reduce or eliminate tumor antigen tolerance, thereby enhancing the immune system's ability to combat metastatic cancer; and (3) expansion of the liver metastasis treatment platform to target tumor-associated lymphoid structures, supporting the immune response at the primary tumor site. Any of these methods may be optionally combined with chemo-immunotherapy for enhanced efficacy.

A drug combination of purinostat mesylate and an analog thereof for preventing and treating multiple myeloma, and the use thereof. Specifically, provided is a three-drug or four-drug combination of purinostat mesylate and an analog thereof, dexamethasone and other drug, which drug combination has significantly enhanced synergistic anti-tumor activity in vitro and in vivo, synergistically inhibits the expression of the key survival protein in multiple myeloma, is superior to existing clinical combination regimens, and has no significant toxic side effects. In addition, the drug combination significantly down-regulates the expression of CDK6, and overcomes the drug resistance to an immunomodulator. In particular, the three-drug combination of puisostat mesylate, a glucocorticoid and an immunomodulator has an excellent prevention and treatment effect on multiple myeloma, especially relapsed / refractory multiple myeloma.

The invention relates to the technical field of genetic engineering and biological agents, in particular to a hybrid peptide with immunoregulation and anti-oxidation functions and a preparation method and application of the hybrid peptide. The polypeptide provided by the invention has immunoregulation and antioxidation functions at the same time, and in a normal or immunosuppression state, the polypeptide can significantly improve the immunologic function of a body and reduce the damage of immunosuppression to the body; the oxidation resistance of cells and organisms can be enhanced; meanwhile, the polypeptide has the advantages of low cytotoxicity, high safety, simplicity and convenience in preparation and low cost, can be used as an ideal immunomodulator and an antioxidant, is widely applied to the fields of medicines, foods, health care, feeds, nutrition and the like of human and animals, and has very good application potential and value.

The invention discloses a fish circRNA and application thereof, the fish is pelteobagrus fulvidraco, the circRNA is named circArid4b, and the nucleotide sequence of the circRNA is shown as SEQ ID NO.1. The invention further discloses a preparation method of the circRNA. The fish circRNA provided by the invention can regulate and control Arid4b expression of a source gene of the fish circRNA under hypoxia and bacterial infection conditions, influence apoptosis pathways and inflammatory reactions, and finally regulate and control antibacterial reactions. The invention further provides an interferent of the circRNA, the circRNA interferent can be used as a fish immunomodulator, infection of Aeromonas veronii on pelteobagrus fulvidraco under the low-oxygen condition is remarkably inhibited, and a new mode is provided for efficiently improving the antibacterial immunity of fish under the low-oxygen environment.

The invention features new a method for treating inflammatory bowel disease, including Crohn's Disease (CD) or ulcerative colitis in a human patient, comprising administering to a patient a combination therapy comprising an anti-α4β7 antibody, a TNFα antagonist, and an immunomodulator.

Provided is the development and use of a novel immunomodulator. The immunomodulator is an antibody or an antigen-binding portion thereof that binds to CCR8. The antibody has a neutralizing activity in blocking CCL1 / CCR8 axis, can inhibit CCL1-induced cell activation, and for low-affinity FcγRIIIA158F allele carriers in the population, enhances the ADCC effect by means of Fc optimization.

Disclosed are compounds of Formula (I′), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing or ameliorating diseases or disorders such as cancer or infections.

The invention discloses an application of a small-molecule inhibitor combined medicine in preparation of a medicine for treating multiple myeloma. The application comprises the step of combining a proteasome inhibitor or an immunomodulator with an STAT3 small-molecule inhibitor. According to the present invention, the killing effect of the STAT3 targeting small molecule inhibitor BBI608 (Napabucasin) on MM cells and MM stem cells is provided, and the STAT3 targeting small molecule inhibitor BBI608 (Napabucasin) is combined with bortezomib (BTZ) or lenalidomide (Len) to improve the synergistic killing effect on multiple myeloma (MM) cells;

This immunomodulation agent contains yeast deposited to the National Institute of Technology and Evaluation under international deposition number NITE BP-04012. Preferably, the immunomodulation agent is for use in modulation of cytokine production. More preferably, the immunomodulation agent modulates the production of a cytokine in macrophage cells or dendritic cells. Further preferably, the immunomodulation agent modulates immunity via TLR2. The cytokine is preferably at least one selected from IL-1β, IL-6, IL-8, IL-10, IL-12, and TNF-α.

The invention discloses a larimichthys crocea IL-22 recombinant protein which is a larimichthys crocea IL-22 mature peptide sequence, and the amino acid sequence of the larimichthys crocea IL-22 recombinant protein is as shown in SEQ ID NO. 2. The recombinant protein is obtained by amplifying and coding gene segments of amino acids from 31st to 190th positions of large yellow croaker IL-22 mature peptide through PCR (Polymerase Chain Reaction), and transforming escherichia coli for heterologous expression. The larimichthys crocea IL-22 recombinant protein can activate a transcription factor STAT3 in a larimichthys crocea head kidney cell line (LYCK) and also can induce expression of inflammatory factors (IL-1beta, IL-6 and IL-8) in immune organs of larimichthys crocea, so that the larimichthys crocea IL-22 recombinant protein has an obvious immunoregulation effect and shows a good application prospect in research and development of aquatic immunomodulators.

The invention discloses an ultralow-viscosity water-in-oil vaccine adjuvant and a preparation method thereof, and the ultralow-viscosity water-in-oil vaccine adjuvant comprises the following components in percentage by weight: 73%-75% of oil for injection, 20%-23% of a compound emulsifier, 2%-7% of a stabilizer, 0.5%-1.5% of a chiral immunomodulator and 1%-2% of a temperature-responsive material, the preparation method comprises the following steps: heating oil for injection as an oil phase; adding the compound emulsifier, the stabilizer, the chiral immunomodulator and the temperature response type material into the oil phase, stirring until the materials are completely dissolved to form a uniform oil phase mixture, slowly adding the water phase into the oil phase mixture, performing high-speed shearing to form primary emulsion, homogenizing the primary emulsion, and performing freeze drying to obtain the chiral immunomodulator. And carrying out emulsion refining by adopting a micro-fluidic technology to obtain the ultralow-viscosity water-in-oil type vaccine adjuvant. The ultra-low viscosity and injection comfort are achieved, precise immunization is achieved for different pathogens, multiple immune pathways are activated at the same time, a wide and lasting protection effect is generated by training an immune mechanism, and the ultra-low viscosity and injection comfort have the intelligent drug release characteristic, excellent stability and broad-spectrum applicability.

The invention provides an efficacy-prolonged new coronavirus self-replicating nucleic acid vaccine, a product capable of being prepared from the vaccine and application of the vaccine. According to the saRNA vaccine provided by the invention, the innate immunomodulator is introduced to improve the immunogenicity of saRNA, so that enough immune response is induced under single-needle inoculation with lower dose, and immune protection on various new coronaviruses and mutants thereof is provided.

Provided are molecules including antibodies binding T cell receptor (TCR). In particular, provided are antibodies binding human γδ TCR, wherein the human γδ T cells can be activated and modulated. Also provided are bispecific tumor-targeting immunomodulators binding to a tumor-associated antigen and γδ T cell receptors simultaneously and enhancing cell-mediated immune response in the treatment of cancer. Methods of making the antibodies, and methods of using the antibodies to kill cancer cells, are also provided.

The invention discloses an application and method of SAH-CIM hydrogel in promoting survival of retinal ganglion cells in glaucoma. The hydrogel comprises a Y-type primitive composed of three DNA chains and a siRNA connector, and the nucleotide sequences of the three DNA chains are SEQ ID NO.1-SEQ ID NO.3; the method comprises the following steps: S1, constructing a Y-type primitive: mixing three DNA chains with equal molar concentration in an annealing buffer solution, performing high-temperature denaturation at 95 DEG C, and then quickly cooling to 4 DEG C to finish annealing, so as to form a stable Y-type structure with three-way cohesive ends; s2, synthesizing a siRNA (small interfering Ribonucleic Acid) connector; and S3, mixing the Y-type element and the siRNA connector according to a molar ratio of 1: 1.5 at room temperature to react for 30 minutes, and forming a three-dimensional network structure through complementary pairing driven self-assembly, thereby finally obtaining the SAH-CIM hydrogel. The SAH-CIM hydrogel provided by the invention can be used for preventing / treating ischemia-reperfusion injury and related diseases, for example, the SAH-CIM hydrogel can be used for treating glaucoma, accurate co-delivery of a neuroprotective agent and an immunomodulator can be realized, and the SAH-CIM hydrogel has the advantages of treatment accuracy and biocompatibility.

The invention relates to crystalline forms of a 3-substituted 1,2,4-oxadiazole compound, including an anhydrous crystalline form, methods of their preparation, and related pharmaceutical preparations thereof. The invention also relates to preparations suitable for pharmaceutical, veterinary, and agriculturally-relevant uses.

The present invention relates to ligands of fibroblast activating protein (FAP) for active delivery of various therapeutic payloads (e.g., cytotoxic drugs, therapeutic radionuclides, proteins, and immunomodulators) at disease sites. In particular, the present invention relates to the development of multivalent FAP ligands for therapeutic applications involving diseases or disorders such as cancer, inflammation or another disease characterized by FAP overexpression.

The invention discloses a targeted enhanced copper death-immunomodulator and a preparation method and application thereof, and belongs to the technical field of medical materials.The targeted enhanced copper death-immunomodulator comprises a polydopamine nanoparticle (PDA) substrate and a CuO2 nano-dot compounded CuO2 PDA nano-composite, the CuO2 PDA nano-composite is wrapped with a cell membrane, and the cell membrane is coated with a polydopamine nano-particle (PDA) substrate and a polydopamine nano-particle (PDA) nano-dot. According to the invention, a targeting ligand of a programmed cell death ligand-1 (Program Cell Death Ligand 1, PD-L1) is grafted on a cell membrane, and the targeting ligand of the Program Cell Death Ligand 1 (PD-L1) is grafted on the cell membrane. The regulator can be efficiently accumulated to a tumor site in a targeted manner, on one hand, the regulator can produce H2O2 in situ in a tumor, the intracellular oxidation-reduction balance is broken, the yield of active oxygen in the tumor is enhanced, and then tumor cell copper death is enhanced; on the other hand, the regulator can durably reduce the abundance of PD-L1 on the surfaces of tumor cells, and finally the purpose of multi-path combined efficient tumor immunotherapy is achieved.

The present invention discloses a preparation method and application of a bacterial bionic vesicle for reprogramming macrophages. The preparation of the bacterial bionic vesicle is to first fuse the bacterial outer membrane anchor protein with the IFN-γ gene, and then use high-pressure homogenization technology to drive genetically engineered bacteria to extrude from the cracks and self-assemble into bacterial bionic vesicles modified with IFN-γ surface. In vitro, the bacterial bionic vesicles of the present invention can promote the reprogramming of M1 macrophages into M2 macrophages, and release nitric oxide to directly kill tumor cells. In vivo, the bacterial bionic vesicles can efficiently enrich in the tumor area by virtue of their nanosize, reprogram the tumor-promoting M2TAMs to the tumor-killing M1TAMs and coordinate adaptive immunity to jointly inhibit tumor growth. In short, the bacterial bionic vesicles of reprogramming macrophages of the present invention are a powerful immunomodulator, which significantly inhibits tumor growth in a variety of tumor models and is of great significance in the immunotherapy of tumors.

This application relates to trans amplifying RNAs encoding immune modulating proteins, and methods of use thereof for payload expression in cells and subjects.

The disclosed method of treating a malignant solid tumor in a subject includes the steps of administering to the subject an immunomodulatory dose of a radioactive phospholipid ether metal chelate, a radiohalogenated phospholipid ether, or other targeted radiotherapy (TRT) agent that is differentially retained within malignant solid tumor tissue, and either (a) performing in situ tumor vaccination in the subject by introducing into at least one of the malignant solid tumors one or more agents capable of stimulating specific immune cells within the tumor microenvironment, or (b) performing immunotherapy in the subject by systemically administering to the subject an immunostimulatory agent, such as an immune checkpoint inhibitor. In a non-limiting example, the radioactive phospholipid ether metal chelate or radiohalogenated phospholipid ether has the formula:wherein R1 comprises a chelating agent that is chelated to a metal atom, wherein the metal atom is an alpha, beta or Auger emitting metal isotope with a half-life of greater than 6 hours and less than 30 days, or wherein R1 comprises a radioactive halogen isotope. In one such embodiment, a is 1, n is 18, m is 0, b is 1, and R2 is —N+(CH3)3.

The present invention relates to pharmaceutical compositions of 1,2,4-oxadiazole compounds or a pharmaceutically acceptable salt thereof of formula (I)In the formula Q is O, R1 is the side chain of Ser, R2 is —CO-Thr, R3 is the side chain of Asn or Glu, and R4, R5 and R6 are each H.

Disclosed are compounds of Formula (I), methods of using the compounds as immunomodulators, and pharmaceutical compositions comprising such compounds. The compounds are useful in treating, preventing, or ameliorating diseases or disorders such as cancer or infections.

The present disclosure provides for a synthetic immunogenic protein for use as an immuno-modulatory agent to enhance mammalian immune reactions towards conjugated protein or peptide containing antigens that are otherwise poorly immunogenic, including but not limited to self-antigens. The chimeric immunogenic proteins of the present disclosure can be used in the treatment of many illnesses, including but not limited to cancers, infectious disease, autoimmune disease, allergies and any clinical indication involving or affected by the immune response of a mammalian host.