45 results about "Immunologic Suppression" patented technology

Disclosed are AAV viral-based vector compositions useful in delivering a variety of nucleic acid segments, including those encoding therapeutic polypeptides to selected mammalian host cells for use in therapeutic autoimmune modalities, including, for example, the in vivo induction of immunological tolerance via a liver-directed AAV-based gene therapeutic regimen for treating and / or ameliorating autoimmune disorders such as multiple sclerosis. Further disclosed are nucleic acid segments encoding therapeutic polypeptides that have been codon-optimized for expression in human cells.

The invention belongs to the technical field of active peptide preparation, and particularly relates to an active collagen peptide with an immunoregulation function and a preparation method and application thereof. The active collagen peptide with an immunoregulation function is prepared by using a method of performing composite enzymolysis and separating and collecting specified collection liquid by using a chromatographic column, and a new thought is provided for improving the immunity; the prepared active collagen peptide can significantly improve the proliferative activity, phagocytic ability and NO secretion amount of RAW264.7 cells and change the cell morphology, has an important regulation effect on immune balance recovery of immunosuppression model mice, and can regulate the problem of low immunologic function of mice induced by cyclophosphamide, regulate immune balance and improve the body immunity.

The invention belongs to the field of biological medicines, and relates to a drug-loaded nano-vesicle as well as a preparation method and application thereof. The drug-loaded nano-vesicle comprises a vesicle core and a drug-loaded nano-vesicle, wherein the vesicle core comprises siRNA (small interfering Ribonucleic Acid) capable of specifically targeting and silencing an NR1D1 gene; the vesicle membrane is formed by fusing an erythrocyte membrane, a macrophage membrane, cardiolipin, cholesterol and lecithin. The drug-loaded nano-vesicle can specifically target macrophages in a sepsis immunosuppression stage, has an intracellular response release function, recovers BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axis functions by inhibiting NR1D1 expression, reconstructs a macrophage phagocytosis function and lysosome-dependent bacterium removal capability, and can be used for preparing a drug-loaded nano-vesicle with a specific targeting function. The survival rate of sepsis immunosuppression model animals is obviously improved; and the bacterial load is reduced. Compared with a traditional electroporation method, the preparation method disclosed by the invention has the advantage that the encapsulation efficiency of siRNA is remarkably improved.

The invention discloses application of apigenin in preparation of a product for treating sjogren syndrome, and belongs to the technical field of medicines. The apigenin is used for remarkably regulating and controlling the immune system of the body, namely enhancing the immunosuppression function of MDSCs of the body, further inhibiting activation of dendritic cells DCs, resulting in reduction of the expression level of B cell activating factors BAFF, finally achieving the purposes of inhibiting B cell differentiation and reducing immunocompetence, and relieving the symptoms of SS.

The present invention relates to a composition for anti-cancer treatment, the composition including immunogenic tumor-derived extracellular vesicles using an endoplasmic reticulum stress inducer, and a method for producing the same. The composition according to the present invention includes extracellular vesicles in which tumor immune-activating protein is increased and immune-suppressive protein is decreased so that immunogenicity is enhanced, and thus can be used as a pharmaceutical composition or a food composition for anti-cancer treatment.

The invention belongs to the technical field of biological medicine, and relates to pharmaceutical application of an oxidative phosphorylation inhibitor, in particular to application of the oxidative phosphorylation inhibitor in preparation of an immunomodulatory drug, and the immunomodulatory drug has the advantages that the function damage of newborn myeloid-derived suppressor cells caused by antagonism BCG (bacillus calmette guerin) vaccination is inhibited, and the immunomodulatory effect is improved. The compound is used for preventing or treating neonatal immune-related diseases caused by bacillus calmette guerin vaccine inoculation. The invention finds that the BCG can cause damage to the immunosuppression function of the MDSC of the suckling mouse through up-regulation oxidative phosphorylation, and the negative effect caused by inoculation of the BCG can be reversed by using the OXPHOS inhibitor, so that the immunosuppression function of the MDSC of the suckling mouse is successfully recovered in an in-vivo and in-vitro model, and the immune-related adverse reaction caused by inoculation of the BCG is expected to be improved.

Methods are provided for enhancing immune responses comprising providing an immunogenic composition comprising a cocktail of an intracellular agonist, an immunosuppressive antagonist, and a cytostatic / damage-inducing agent. Further provided herein are methods for treating primary tumors and preventing metastasis.

This disclosure relates to an immunoglobulin single variable domain (ISVD)-containing modulator that allosterically binds to a three-dimensional (3D) epitope of a protein complex comprising at least one inhibitory immune receptor and at least one corresponding ligand. The modulator regulates cooperativity within such complexes, thereby affecting the binding affinity and downstream signaling pathways. Specifically, the allosteric modulator of this invention induces positive cooperativity in immunoinhibitory receptor-ligand complexes, thus suppressing immune responses in a spatiotemporally restricted manner. Accordingly, these allosteric modulators are useful as therapeutic agents for inflammatory diseases, such as autoimmune diseases, allergic diseases, or graft-versus-host disease (GVHD). Moreover, this disclosure pertains to methods for identifying, selecting, and producing said allosteric modulators.

Soluble TREML1 is involved in many inflammatory diseases and plays an important role in immune suppression. Soluble TREML1 can bind the l-domain of CD11 b and induce an immune suppressive phenotype. Thus, soluble TREML1 may be a good target for treating inflammatory diseases. The present invention relates to antibodies that can reduce soluble TREML1 binding to CD11b+ immune cells and their uses for reversing TREML14nduced immune suppression. Anti-TREML1 antibodies provide a novel and potential therapy for these disease conditions such as cancer.

The application belongs to the field of biological medicine, and relates to a drug-loaded nanovesicle and a preparation method and application thereof. The drug-loaded nanovesicle comprises: a vesicle core comprising siRNA capable of specifically targeting a silenced NR1D1 gene; and a vesicle membrane fused by red blood cell membranes, macrophage membranes, cardiolipin, cholesterol and lecithin. The drug-loaded nanovesicle can specifically target macrophages in the immune suppression stage of sepsis, and has an intracellular response release function. By inhibiting the expression of NR1D1, the drug-loaded nanovesicle restores the functions of BMAL1 and IGF2BP2-ATP6V1B2 / ATP6V0c axes, reestablishes the phagocytosis function of macrophages and the lysosome-dependent bacterial clearance capacity, significantly improves the survival rate of animals in a sepsis immune suppression model and reduces the bacterial load. Compared with a traditional electroporation method, the preparation method of the application significantly improves the encapsulation rate of siRNA.

The invention belongs to the technical field of biological medicine, and particularly relates to application of UFL1 gene in preparation of a product for regulating and controlling tumor immune escape. The invention provides an application of a UFL1 gene in preparation of a product for regulating and controlling tumor immune escape. A nucleotide sequence of the UFL1 gene is shown as SEQ ID NO. 1; the tumors include pancreatic cancer. By taking UFL1 as a target spot and knocking out the UFL1 gene, the quality and volume of pancreatic cancer can be inhibited, and the proportion of CD8 + T cells and the level of immune cell factors can be improved; the proportion of immunosuppression Treg, MDSCs and M2 type macrophages is reduced, and the tumor immune microenvironment is regulated and controlled, so that the immune escape of the tumor is inhibited.

Provided herein are methods for enhancing an immune response comprising providing an immunogenic composition comprising a mixture of an intracellular agonist, an immunosuppressive antagonist, and a cell inhibitor / damage inducer. Further provided herein are methods of treating a primary tumor and preventing metastasis.

A protein nanospheres and method to treat dysfunction from chemotherapy and immunosuppressive therapy, and a manufacture of fibrinogen-coated albumin spheres (FAS) and High-Fibrinogen Spheres (HFS) which have higher concentrations of fibrinogen molecules per sphere than FAS, and their use for medical treatments. Both kinds of nanoparticles are effective in the mitigation of the toxic effects of certain chemotherapeutic and radiological agents that are typically used in the treatment of cancer, or the treatment of autoimmune diseases, or for patients with both diseases. FAS and HFS can exert their beneficial effects via a variety of mechanisms which match the need of the body for specific cell types, including any of the subgroups of T cells and antibody producing cells, the relative concentration of each kind is vital to the balance between tumor surveillance and autoimmune disease suppression.

The application relates to a composite nanogel and a preparation method and application thereof, in particular to the technical field of biomedical materials. The composite nanogel comprises a nanogel framework and tirapazamine and folic acid loaded on the nanogel framework, wherein raw material components of the nanogel framework comprise a temperature-sensitive monomer and a monomer containing a catechol group. The composite nanogel provided by the application can solve the problems that poor blood vessel adhesion of traditional embolic agents easily leads to embolism recanalization, simple physical embolism is difficult to completely remove hypoxic tumor cells, and existing treatment strategies cannot effectively reverse the immune suppression microenvironment after embolism and activate the systemic anti-tumor immune response.

The present invention belongs to the field of biomedicine and materials, and specifically relates to a protein-coupled imidazoquinoline compound and a synthesis method and application thereof. The present invention aims at the problem that imidazoquinoline agonists have large toxic side effects and are prone to cause cytokine storms when used in vivo. By coupling the active amino group of the imidazoquinoline agonist with albumin, which has low human immunogenicity, good biosafety and accumulation advantage at tumor sites, through a reduced glutathione-responsive linker, the targeting and responsive release at the tumor site are achieved, thereby reducing systemic nonspecific toxicity, reducing the possibility of causing cytokine storms, improving the immunosuppressive microenvironment of the tumor, activating anti-tumor immunity, and achieving better therapeutic effects and biosafety.

Described herein are compositions and methods of use thereof for reducing inhibiting B cell activation, B cell proliferation, the production of pathologic, autoimmune or interfering antibodies; and / or for eliciting humoral suppression and / or B cell tolerance in a subject in need thereof by contacting immune cells of the subject or donor immune cells in vivo and / or ex vivo with a composition comprising a Butyrophilin, optionally Butyrophilin A2, or a conjugate or fusion protein comprising said Butyrophilin. The methods include the use of butyrophilin A2 (BTN2A2), a BTN2A2 fragment thereof, a BTN2A2- related isoform, or a BTN2A2-related isoform fragment, or conjugates, and fusion polypeptides containing, preferably which comprise an Fc region comprising one or more mutations which reduce FcR binding and / or which suppress FcRN mediated clearance.

The invention provides a calmodulin B subunit mutant and application of the calmodulin B subunit mutant in preparation of universal immune effector cells. The CNB mutant disclosed by the invention can be used for antagonizing the blocking of CsA, FK506 or volocinorin on an NFAT signal channel; meanwhile, the compound has drug resistance to CsA, FK506 and volocinorin at the same time. The CNB mutant disclosed by the invention is expressed into a universal immune effector cell, and when the CNB mutant is combined with an immunosuppressive drug to treat tumors or autoimmune diseases, the activity of a T cell of a patient can be reduced, so that rejection reaction of the patient to the heterologous universal immune effector cell is avoided, and the curative effect of the heterologous universal immune effector cell is improved. Colonization of universal immune effector cells in the body of a patient is improved, and the treatment effect of the universal immune effector cells is achieved. Meanwhile, after the treatment is finished, the universal immune effector cells can be repelled after the immune system of the patient is recovered, so that the strategy that the immune cells are removed after the treatment becomes possible, and the safety of the immune cell therapy can be greatly improved.

The present invention relates to a method for efficiently differentiating neural stem cells into astrocytes and, more particularly, to a cell conversion-based method for more efficiently differentiating human neural stem cells into astrocytes that exhibit immune response suppression ability within a short period of time. Unlike a conventional method, the method for differentiating neural stem cells into astrocytes by using a differentiation medium containing a combination of several cytokines, according to the present invention, involves a shortened differentiation time and has excellent differentiation efficiency, and the differentiated astrocytes exhibit immune response suppression ability, and thus can be useful as an agent for treating various brain diseases such as degenerative neurological diseases.

Use of naphthoquine phosphate in preparation of a medicament for treating autoimmune diseases. It is proved in a mouse rheumatoid arthritis model that the intragastric administration of naphthoquine phosphate can remarkably ameliorate symptoms such as joint redness, swelling, and deformities and reduce the levels of antigen-specific antibodies. It is proved in a mouse systemic lupus erythematosus model that the intragastric administration of naphthoquine phosphate can remarkably reduce the levels of anti-double-stranded DNA antibodies and anti-nuclear antibodies. Pharmacodynamic and pharmacological studies prove that naphthoquine phosphate has ideal immunosuppressive activity and can be used to prepare the medicament for treating autoimmune diseases. Further provided is a pharmaceutical use of naphthoquine phosphate in the treatment and auxiliary treatment of rheumatoid arthritis or systemic lupus erythematosus. The medicament is a pharmaceutical composition consisting of a therapeutically effective amount of naphthoquine phosphate serving as an active ingredient and pharmaceutical excipients.

Recent studies indicate that sIL7R is involved in the development of autoimmune diseases. The present invention provides methods and compositions for a novel antibody therapeutic against the soluble isoform of the interleukin 7 receptor (sIL7R), a potent driver of self-destructive immune responses that cause autoimmune diseases including multiple sclerosis, lupus nephritis, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, and many other autoimmune diseases. The present invention includes antibodies specific for sIL7R that inhibit SIL7R, a driver of autoimmunity, without inhibiting mIL7R, thereby reducing the severity of or preventing autoimmunity without activating immunosuppressive mechanisms.

The present disclosure provides, for instance, a method of inhibiting resistance to a DDR inhibitor in a subject, the method comprising administering to the subject a GDF15 inhibitor, thereby inhibiting resistance to the DDR inhibitor in the subject. The disclosure also provides combination therapies for cancer, comprising co-administration of a DDR inhibitor and a GDF15 inhibitor.

This disclosure relates to the combination of soluble β-glucan and immune suppression-relieving agents that affect the tumor microenvironment. Soluble β-glucan promotes an immunostimulatory environment, which allows enhanced effectiveness of anti-angiogenics, checkpoint inhibitors including non-tumor targeting antibodies.

The invention belongs to the technical field of medicines, and particularly relates to a pharmaceutical composition for treating headache and a preparation method thereof. The pharmaceutical composition comprises the following raw materials in parts by weight: 30-40 parts of a pharmaceutical active component, 2-4 parts of a disintegrating agent, 6-11 parts of a filler and 0.2-0.5 part of a lubricant, the active pharmaceutical ingredient consists of porphyridium polysaccharide and manganese gluconate in a mass ratio of 1: (0.5-1). The action mechanisms of the two active components in the pharmaceutical composition are clear and complementary: porphyridium polysaccharide reduces the expression of a proinflammatory factor by inhibiting an NF-kappa B signal channel so as to relieve the stimulation to trigeminal nerve endings, and the porphyridium polysaccharide is mild in action and can avoid the potential influence of strong immunosuppression on the immune system of children; manganese gluconate blocks a CGRP receptor in a targeting manner, directly inhibits nerve ending sensitization and central pain signal transduction mediated by the pain-inducing peptide, and intervenes migraine attack from a key path.

The invention relates to composite nanogel as well as a preparation method and application thereof, in particular to the technical field of biomedical materials. The composite nanogel comprises a nanogel skeleton, tirapazamine and folic acid, the tirapazamine and the folic acid are loaded on the nanogel skeleton, and raw material components of the nanogel skeleton comprise a temperature-sensitive monomer and a monomer containing a catechol group. The composite nanogel provided by the invention can solve the problems that a traditional embolism agent is poor in blood vessel adhesion and easy to cause embolism recovery, hypoxia tumor cells are difficult to thoroughly remove by pure physical embolism, and an immunosuppressive microenvironment after embolism cannot be effectively reversed and systemic anti-tumor immune response cannot be activated by an existing treatment strategy.

Novel compounds that are improved analogs and mimetics of DSHN and methods to treat or inhibit cancer using the compounds. The methods can require lower doses than for DSHN and the compounds can have a larger biological maximum than DSHN. Nuclear receptor NR0B2 is activated by the disclosed compounds to reduce immune-suppressive Tregs, thereby attenuating tumor growth and metastasis. The therapy disclosed herein results in an inhibition of Treg expansion and an expansion of cytotoxic T cells. This therapy can significantly reduce tumor growth with lower doses compared to other available treatments.

Compositions of matter and treatment protocols for reducing or completely avoiding the need for immune suppression in the context of allograft or xenograft transplantation. Use of mesenchymal stem cells, manipulated mesenchymal stem cells, iPSC derived mesenchymal stem cells, and products of said mesenchymal stem cells for promoting the process of immunological tolerance. In one embodiment the invention provides the use of third party “universal donor” iPSC gene edited mesenchymal stem cells to promote tolerance in context of a solid organ transplant such as renal, cardiac, hepatic or small intestine. In other embodiments endogenous mesenchymal stem cells in composite tissue allografts are activated and / expanded in order to promote tolerogenesis and reduced need for immune suppression.

Use of naphthoquine phosphate in preparation of a medicament for treating autoimmune diseases. It is proved in a mouse rheumatoid arthritis model that the intragastric administration of naphthoquine phosphate can remarkably ameliorate symptoms such as joint redness, swelling, and deformities and reduce the levels of antigen-specific antibodies. It is proved in a mouse systemic lupus erythematosus model that the intragastric administration of naphthoquine phosphate can remarkably reduce the levels of anti-double-stranded DNA antibodies and anti-nuclear antibodies. Pharmacodynamic and pharmacological studies prove that naphthoquine phosphate has ideal immunosuppressive activity and can be used to prepare the medicament for treating autoimmune diseases. Further provided is a pharmaceutical use of naphthoquine phosphate in the treatment and auxiliary treatment of rheumatoid arthritis or systemic lupus erythematosus. The medicament is a pharmaceutical composition consisting of a therapeutically effective amount of naphthoquine phosphate serving as an active ingredient and pharmaceutical excipients.

Methods are provided for enhancing an immune response comprising providing an immunogenic composition comprising a cocktail of intracellular agonists, immune inhibition antagonists, and cytostatic / damage-inducing agents. Further provided herein are methods of treating a primary tumor and preventing metastasis.

The application discloses a use of an active ingredient in repairing heart tissue damage. Specifically, the application discloses an active ingredient which can be used for repairing heart tissue damage and treating diseases related to lymphatic vessel abnormalities, and the active ingredient comprises a TBX1 protein, a coding sequence of the TBX1 protein, or a promoter of the TBX1 protein, or a combination thereof. The TBX1 protein can promote the proliferation of heart lymphatic vessel endothelial cells, play an immune regulation role, promote the establishment of an immune inhibition microenvironment in myocardium after heart tissue damage, inhibit an autoimmune reaction after the heart tissue damage, relieve concurrent heart tissue inflammation, and promote the repair and regeneration of the damaged heart tissue.

The invention belongs to the technical field of biological medicines, and particularly relates to a preparation method and application of a small molecular compound targeting tumor mitochondria. The structural formula of the tumor mitochondria targeting small molecule compound is a small molecule compound CYN-CDA, and the small molecule compound CYN-CDA can improve the high-expression immunosuppression microenvironment of tumor CD47 and PD-L1, and the efficacy of the small molecule compound CYN-CDA is 300 times that of CDA. The CYN-CDA not only solves the bottleneck of tumor immunotherapy, but also starts a multi-mode anti-tumor therapy of immunotherapy and collaborative radiotherapy. The CYN-CDA coated Alb nano preparation formed by self-assembly of a small molecule compound CYN-CDA and albumin has the characteristics of strong tumor mitochondria targeting property, high copper depletion efficiency and the like.