49 results about "Immuno suppression" patented technology

The invention discloses a dynamic identification method for unusual cells before young tumors based on multi-omics data, and relates to the technical field of cell unusual identification. A dynamic correlation intensity matrix and a cumulative effect contribution matrix are constructed, a differentiation screening strategy is implemented according to individual response characteristics, and the unusual cells before young tumors are identified. And the abnormal dynamic high-fidelity identification of the young tumor pre-cells is realized. And aiming at individuals of different response types, an instant path, a long-term path or a double-path fusion strategy is respectively adopted, key behavior data is accurately screened, and the input quality is improved. According to the method, redundant interference is effectively eliminated, the simulation capability of the model on key processes such as immunosuppression and DNA damage accumulation is enhanced, the biological rationality and prediction precision of a cell state evolution sequence are remarkably improved, and the problems of model response lag, low calculation efficiency and output distortion caused by data noise in the prior art are solved; and a reliable technical support is provided for early warning and individualized intervention of precancerous lesions.

The invention discloses an anti-aging and anti-allergy spray suitable for pregnant women based on micro-ecology-barrier-immune synergistic repair and a preparation method of the anti-aging and anti-allergy spray. The spray is prepared from 2.00 percent to 4.00 percent of hydrolyzed quinoa protein, 1.00 percent to 5.00 percent of lactobacillus / soybean milk fermentation filtrate, 0.30 percent to 1.00 percent of radix stellariae extract, 0.20 percent to 1.50 percent of perilla leaf extract, 0.01 percent to 0.50 percent of three-layer liposome tetrahydrocurcumin, 1.00 percent to 10.00 percent of Tibetan plateau freeze-dried tricholoma matsutake extracting solution, an active peptide combination and a ceramide compound. According to a quadruple synergistic mechanism, (1) the pH value of the fermentation filtrate is adjusted to 5.3, and the fermentation filtrate and the hydrolyzed quinoa extract synergistically construct a micro-ecological foundation; (2) repairing the barrier by ceramide NP, cholesterol, phytosphingosine and the like; (3) multiple anti-allergy effects of radices stellariae dichotomae, purple perilla, asiaticoside and dipotassium glycyrrhizinate; and (4) liposome curcumin, glabridin liposome and active peptide cooperate to resist aging, and a'micro-ecological balance-barrier reconstruction-immunosuppression-targeted anti-aging 'quadruple synergistic effect system is constructed. The preparation method comprises the steps of A-phase / B-phase preparation, emulsification, active addition and sterile filling, and the skin requirements in the pregnancy period and the lactation period are met.

The invention relates to miRNA, a miRNA simulant and a delivery system of the miRNA simulant, and belongs to the field of biological medicine. The sequence of the miRNA or the miRNA simulant is as shown in SEQ ID NO. 1. It is found for the first time that the miRNA or miRNA simulant can effectively inhibit immune escape and treat immunosuppressive cancers when being independently used as an active component. According to the invention, the miRNA or miRNA simulant is further combined with a photoresponsive plant exosome platform, so that the stability and delivery efficiency of the miRNA in a tumor microenvironment are improved, time-space precise release can be realized through light activation, and cancer cells and immunosuppressive cells driven by the cancer cells, such as M2 type macrophages, Treg and the like, can be effectively targeted. The strategy shows the comprehensive advantages of high efficiency, safety, controllability, personalized customization and the like, and has the potential of serving as a cancer therapeutic agent.

The invention discloses application of mitoxantrone in preparation of an anti-rabies virus drug, reveals that clinical anti-tumor and immunosuppression drug mitoxantrone has remarkable anti-rabies virus activity for the first time, and opens up a new application field for mitoxantrone. The rigorous in-vitro and in-vivo tests prove that the mitoxantrone can inhibit virus replication in a dose-dependent manner, reduce virus gene and protein expression and remarkably improve the survival rate of infected mice in an animal model. The invention provides a new clinical application approach for mitoxantrone, provides a powerful candidate drug and a brand-new technical scheme for anti-rabies virus drugs, and has important practical significance and clinical application prospects for coping with rabies which is a major public health threat.

The application discloses a kind of young tumor pre-cell abnormal dynamic identification method based on multi-omics data, it is related to cell abnormality identification technical field, the application is by constructing dynamic correlation strength matrix and cumulative effect contribution matrix, according to individual response characteristics Implementation of differentiating screening strategy, realize the high fidelity identification of young tumor pre-cell abnormal dynamics.For different response type individuals, respectively using instant path, long-term path or double-path fusion strategy, accurately screening key behavior data, improve input quality.The method effectively eliminates redundant interference, enhances the model's ability to simulate key processes such as immune suppression and DNA damage accumulation, significantly improves the biological rationality and prediction accuracy of cell state evolution sequence, solves the model response lag, low computational efficiency and output distortion problems caused by data noise in the prior art, and provides reliable technical support for early warning and individualized intervention of pre-tumor lesions.

The invention discloses a novel RNA (Ribonucleic Acid) nano vaccine for preventing and treating colorectal cancer as well as a preparation method and application of the novel RNA nano vaccine. According to the nano vaccine, biodegradable polylactic acid-glycolic acid copolymer nano particles are taken as a carrier, and full-tumor cell RNA is encapsulated by a multiple emulsion solvent evaporation method to form the nano vaccine RNA (at) PLGA; the nano vaccine can effectively protect RNA, shows an excellent tumor inhibition effect and good safety in an animal model, can reverse the immunosuppression state of a tumor microenvironment, and provides a new effective strategy for immunotherapy of colorectal cancer.

The invention discloses a method and a pharmaceutical composition for inhibiting tumor growth by combining an mRNA vaccine and a transforming growth factor-beta (TGF-beta) antibody. The medicine composition comprises an mRNA vaccine for coding a tumor specific antigen and a monoclonal antibody for specifically targeting TGF-beta, and tumor specific immune response induced by the mRNA vaccine is combined with the effect of the TGF-beta antibody for relieving tumor microenvironment immunosuppression, so that the killing ability of a body to tumor cells is remarkably enhanced; the compound provided by the invention can effectively inhibit tumor growth and prolong the lifetime of tumor-bearing individuals, has good safety and tolerance, and provides a new effective strategy for tumor treatment.

The inventors have prepared a novel anti-Cath-D antibody (F1M1) that can reduce tumor growth in a Cath-D secreting basal-like TNBC cell line with strong immune infiltration, without significant toxicity. The F1M1 antibody prevents recruitment of immunosuppressive M2 polarized tumor-associated macrophages (TAMs) and induces activation of natural killer cells in the tumor, and the F1M1 also enhances activation of antitumor M1 polarized TAM, recruitment and maturation of conventional cDC1 dendritic cells in the tumor to promote antigen presentation and reduce depletion marker expression of CD4 + and CD8 + T cells in the tumor and drainage lymph nodes. It is worthy of noting that the affinity of the antibody F1M1 to Cath-D is better than that of the antibody F1 prepared by the inventor in advance. The inventors also have prepared a novel Fc-optimized F1M1-Fc + human antibody which can promote ADCC induction of cancer cells and CAF, improve anti-tumor efficacy, and trigger recruitment, activation and cytotoxic activity of NK cells in tumors. The F1M1-Fc + F1M1-Fc + can inhibit the growth of MDA-MB-231 and SUM159 TNBC cell xenografts and two TNBC-PDX (one of the TNBC-PDX is resistant to neoadjuvant chemotherapy), and has no obvious toxicity. In addition, the F1M1-Fc < + > improves the treatment effect of the paclitaxel and enzalutamide combined medicine. Thus, the present invention relates to anti-cathepsin-D antibodies and their use in the treatment of cancer, in particular triple negative breast cancer.

The present invention relates to the field of adoptive immune cell therapy, in particular adoptive T cell therapy. The present invention provides a conversion receptor which is capable of effectively converting an immunosuppressive signal of TGF [beta], which is normally present in the hostile tumor environment of a solid tumor, into a co-stimulatory signal, thereby improving T cell activation, and which can be safely used in therapy. Also provided are nucleic acids encoding the transforming receptors, cells expressing the receptors and pharmaceutical compositions comprising the cells, in particular for the treatment of cancer or infectious diseases, such as adoptive T cell therapy by solid tumors.

The application provides a kind of bionic nanocomposite and its application, the bionic nanocomposite includes nanoparticle, drug and cell membrane;The nanoparticle is loaded as carrier The drug, the cell membrane is coated on the surface of nanoparticle;The particle size of the bionic nanocomposite is 80-130nm;The nanoparticle is mesoporous silica nanoparticle, the drug is bee toxin, and the cell membrane is cancer cell membrane.The bionic nanocomposite of the application has high selectivity, low toxicity and strong antitumor effect, through the mechanism of relieving Fn-induced tumor suppression microenvironment and activating tumor-specific immunity to exert antitumor effect, further elucidate the role of targeted nucleic acid bacillus in the treatment of colorectal cancer and the synergistic therapeutic effect of simultaneous targeting and removing Fn and tumor cell strategy, thereby providing zoological basis and related data for further human clinical application research, providing an important reference for subsequent pathogenic bacteria killing and immune suppression microenvironment improvement combined immunotherapy, which helps to improve the immunotherapy effect of patients with colorectal cancer, and has strong clinical transformation value.

The application provides an in-situ injectable mRNA-hydrogel microsphere complex, a preparation method and application thereof, and belongs to the technical field of biological medicine. The application constructs an injectable mRNA / sgRNA lipid nanoparticle-gel micro-complex, which is used for functionally reprogramming immune-suppressed macrophages in situ at a lesion, and aims to simultaneously strengthen the bactericidal capacity and restore the immune activation function. The encapsulation of the hydrogel microspheres makes the LNP stably stay at the lesion site, and the released phosphatidylserine modified LNP can realize selective delivery to macrophages through TAM receptors. The knockout of MerTK enhances the phagocytic capacity of macrophages and activates the pro-inflammatory signaling pathway, and the delivery of LL-37 mRNA realizes the continuous secretion of antibacterial peptides, thereby significantly enhancing the bactericidal effect. The in-vitro and in-vivo experimental results show that the LMP can realize precise positioning expression at the lesion site, significantly enhance the phagocytic activity, intracellular clearance capacity and antigen presentation function of macrophages, thereby overall inhibiting the progress of implant-related infection.

The invention discloses a PD-L1 cell targeting fusion protein connected in series with a TGFBR2 extracellular domain, IL-2 and a receptor thereof, and an application thereof. Belongs to the technical field of biology. The fusion protein provided by the invention is a heterotetramer formed by connecting two similar heavy polypeptide chains and two similar light polypeptide chains through a disulfide bond. The fusion protein realizes triple functions through a single molecule: tumor specific localization is realized through PD-L1 targeting VHH (Vascular Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus Haemophilus); an immunosuppressive factor TGF-beta in a tumor microenvironment is neutralized through TGFBR2 ECD; effect immune cells expressing a medium affinity IL-2 receptor are selectively activated and amplified by the combination of IL-2 and IL-2R alpha. The PD-L1 inhibitor provided by the invention overcomes the multiple problems of limited curative effect of a single drug, high IL-2 systemic toxicity, tumor microenvironment immunosuppression and the like in the existing PD-(L) 1 inhibitor, and provides technical support for detection, prevention and treatment of PD-L1 positive tumors.

The invention provides a recombinant mesenchymal stem cell for immunoregulation and application of the recombinant mesenchymal stem cell in preparation of a product for preventing and / or treating septicopyemia, relates to the technical field of biological medicines, and aims to improve the expression quantity of IDO1 in a receptor mesenchymal stem cell to obtain the recombinant mesenchymal stem cell. The IDO1 expression level and enzyme activity of the MSC are remarkably improved through a genetic engineering means, meanwhile, the expression levels of TSG6, PTGS2, IRF1 and IL-10 are remarkably increased, it is indicated that the immunoregulation program of the MSC is comprehensively activated, and the immunosuppression effect of the MSC is enhanced; animal tests prove that the recombinant mesenchymal stem cells inhibit systemic inflammatory response, significantly reduce the death rate of septicopyemia mice, promote immune homeostasis recovery, avoid side effects caused by excessive immunosuppression, and realize a bidirectional immunoregulation effect.

Systems and methods to modulate the activation state of immune cells in vivo are described. The systems and methods can be used to transform immunosuppressive macrophages that support cancer growth and metastasis into highly activated tumoricidal macrophages.

The invention discloses an in-vitro activation amplification solution for multiple immune cells as well as a preparation method and application of the in-vitro activation amplification solution. The in-vitro activation amplification solution is prepared from the following components in concentration: 10 to 40 [mu] g / mL of lycium barbarum polysaccharide, 10 to 20 [mu] g / mL of ganoderma lucidum polysaccharide, 3 to 10 [mu] M of ophiopogonin D, 200 to 400 [mu] M of an SCFAs mixed solution, 2 to 10 [mu] g / mL of nisin, 5 to 20 [mu] M of resveratrol, 0.05 to 0.2 [mu] g / mL of a PD-1 antibody and 30 to 60 nM of sodium selenite. According to the in-vitro activation amplification liquid for the multiple immune cells, the components have a synergistic effect, and the anti-tumor function is outstanding. The balanced proportion of the amplification liquid enables the killing rate of immune cells to HepG2 to reach 56%, the DC maturation rate to be 64%, the NK / CD8 + T activation rate to be 68% / 66% and the IFN-gamma secretion to be 400 pg / mL, all the components have the synergistic effect of activating metabolism through SCFAs, enhancing antigen presentation through traditional Chinese medicine polysaccharide, improving drug delivery through nanoparticles and relieving immunosuppression through antibodies, and the problem that the activation efficiency of a single component is low is solved.

The present invention relates to an engineered immune cell, wherein the expression of FKBP12 is inhibited or silenced, and an exogenous chimeric antigen receptor and / or immunosuppressive molecule are expressed. The present invention also provides a composition comprising the engineered immune cell and use thereof in the treatment of cancers, infections, or autoimmune diseases.

Small molecule AhR ligands are disclosed. The ligands can induce the differentiation of Tr1 cells to suppress pathogenic immune responses without inducing nonspecific immune suppression. Methods of treatment of autoimmune diseases using the AhR ligands are also disclosed.

The present invention relates to compositions and methods for generating a nucleic acid delivery system comprising a nucleic acid sequence encoding a heterologous protein comprising a canine tumor-specific antigen (canine melanoma polyepitope (K9Melapoly)) and an inhibitor of an immuno-inhibitory pathway (HSV-1 gD). Additionally, the current invention includes compositions and methods of treating and / or preventing or immunizing a canine against melanoma, and methods of inducing an effector and memory T cell immune response in a canine administered the nucleic acid delivery system of the invention. Furthermore, the invention encompasses a pharmaceutical composition for vaccinating a canine as well as a protein expression system.

Small molecule AhR ligands are disclosed. The ligands can induce the differentiation of Tr1 cells to suppress pathogenic immune responses without inducing nonspecific immune suppression. Methods of treatment of autoimmune diseases using the AhR ligands are also disclosed.

The present invention relates to a glycosylated Fc variant with improved selective binding affinity to FcγRIIIa. Compared to conventional antibodies approved as antibody therapeutic agents, novel human antibody Fc domain variants of the present invention have reduced binding affinity to FcγRIIb, which is an immuno-inhibitory receptor, have improved binding affinity to FcγRIIIa (an increase in the A / I ratio), which is an immuno-activating receptor, thereby having a remarkably improved ability to induce ADCC, and have the effect of maximizing the immune action mechanism of therapeutic protein drugs, and thus can be effectively used in antibody drugs.

The invention belongs to the technical field of mosquito-borne infectious disease prevention and control, and provides an effect of human defensin in inhibition of anopheles sterneri malarial. According to the invention, the human defensin 5 is injected into the body of the anopheles stellari model by adopting a method for constructing the anopheles stellari infection model, and the influence of the human defensin 5 on the malarial transmission capability of the anopheles stellari is evaluated. Results show that after entering the mosquito body, the human defensin 5 inhibits the development of plasmodium johnsonii in the anopheles stersonii at an early stage by stimulating the innate immunity of the mosquito, so that the purpose of reducing the malarial transmission capability of the anopheles stersonii is achieved.

The present application relates to a composition and application for enhancing mesenchymal stem cell treatment efficiency, and belongs to the technical field of cell drug treatment. The composition for enhancing mesenchymal stem cell treatment efficiency comprises a PARP inhibitor and an inflammatory factor. The mesenchymal stem cells are pretreated by the composition, and the mesenchymal stem cells with enhanced treatment efficiency are obtained, which are used for preparing a therapeutic drug for immune diseases characterized by abnormal inflammatory response. The mesenchymal stem cells are treated by the PARP inhibitor combined with the inflammatory factor in the present application, which can improve the intracellular signal transduction and the phosphorylation level of STAT1, increase the expression of the immune suppressor IDO1 and PD-L1, thereby enhancing the immune regulation function of the stem cells, and realizing the gain effect on the treatment of immune diseases mainly characterized by abnormal inflammatory response.

Provided herein are biomarkers that are useful in various aspects of treating and preventing complications and side effects associated with a disease or disorder, such as those associated with immune suppression, disruption of the gastrointestinal microbiome, infections (e.g., bloodstream infections), and / or GvHD, for example, in HSCT subjects. In some aspects, the biomarkers provided herein can be used in identifying a subject who is responding to a bacterial composition and / or subjects that are suitable for a treatment with a bacterial composition.

A novel binding molecule or a fragment thereof and uses thereof are disclosed. The novel binding molecule or a fragment thereof specifically bind to an extracellular translationally controlled tumor protein (TCTP). The binding molecule and the fragment thereof can be used to diagnose, treat, or prevent cancer. The binding molecule and the fragment thereof can be used to alleviate or prevent immune suppression in a tumor immune microenvironment. The binding molecule and the fragment thereof can be used to diagnose, treat, or prevent cancer in a patient who has no response, has a limited response, or is likely to have such a response to treatment using a cancer immunotherapeutic agent.

The application provides a lung cancer immune suppression state evaluation method based on lymphocyte subgroups, and belongs to the technical field of immune suppression state evaluation.The application performs PHATE algorithm manifold dimension reduction and Harmony batch effect correction on high-dimensional data obtained by multicolor flow cytometry, retains the global topological structure of rare lymphocyte subgroups, eliminates cross-batch systematic deviation, extracts batch-invariant cell representation through an adversarial domain adaptive network, identifies lymphocyte subgroups by using graph clustering analysis and constructs a patient-level immune phenotype feature vector, performs Kalman filtering on multi-time-point longitudinal data to build a time series state space model, and finally jointly optimizes the clustering threshold and the routing gating threshold through an artificial intelligence model and a game optimization framework, so that the technical problem of missing detection of rare lymphocyte subgroups caused by systematic deviation during cross-batch integration of multi-batch high-dimensional flow cytometry data is solved.

As described below, the present invention features genetically modified immune cells having enhanced anti-neoplasia activity, resistance to immune suppression, and decreased risk of eliciting a graft versus host reaction, or a combination thereof. The present invention also features methods for producing and using these modified immune effector cells.

This invention provides a calcineurin B subunit mutant and its application in the preparation of universal immune effector cells. The CNB mutant of this invention can antagonize the blocking of the NFAT signaling pathway by CsA, FK506, or voclosporin; and simultaneously exhibits resistance to CsA, FK506, and voclosporin. Expressing the CNB mutant of this invention into universal immune effector cells, when combined with immunosuppressive drugs to treat tumors or autoimmune diseases, can reduce the activity of the patient's own T cells, thereby avoiding the patient's rejection of heterologous universal immune effector cells and improving the colonization and therapeutic effect of universal immune effector cells in the patient's body. Furthermore, after treatment, the universal immune effector cells can be rejected after the patient's immune system recovers, making the strategy of discontinuing immunotherapy after treatment possible, which can greatly improve the safety of immunotherapy.

The application provides a recombinant oncolytic virus, a preparation method and a use thereof, wherein the recombinant oncolytic virus is rVSV M51R mIL27, in the application, by introducing IL-27 into the oncolytic vesicular stomatitis virus, on the one hand, the oncolytic vesicular stomatitis virus can be used as a delivery carrier to continuously express IL-27 in the tumor part, improve the effective concentration of IL-27 in the tumor microenvironment, and avoid systemic toxic side effects; on the other hand, IL-27 can synergize with the immune cell death induced by the oncolytic vesicular stomatitis virus to further enhance the antigen-specific T cell response and promote the transformation of tumor-infiltrating lymphocytes from an exhausted state to an effector state. Meanwhile, IL-27 helps to reshape the tumor immune microenvironment by inhibiting the immune suppressive cell population, thereby improving the overall immune response level. Therefore, the recombinant oncolytic virus provided in the application realizes multi-dimensional immune regulation of the tumor microenvironment through virus-mediated targeted delivery and continuous expression, thereby significantly improving the anti-tumor effect of the oncolytic virus therapy.

This invention belongs to the field of biotechnology, specifically relating to a biomarker for diagnosing immunosuppressive status in chronic tuberculosis and its application. The biomarker is arginase-1. This invention demonstrates that serum Arginase-1 levels are significantly elevated in the progression of chronic tuberculosis, and are significantly positively correlated with the enrichment ratio of myeloid-derived suppressor cells and the expression levels of T cell exhaustion markers. As a key effector molecule of MDSCs, high expression of Arginase-1 reflects abnormal arginine metabolism and T cell exhaustion caused by MDSC amplification, making it an ideal indicator for assessing the immunosuppressive microenvironment in chronic tuberculosis. Using the biomarker of this invention, serum samples can be detected by simple methods such as ELISA, enabling rapid diagnosis, stratification, and dynamic monitoring of the immune status of patients with chronic tuberculosis.

The invention relates to a combination therapy for treating liver cancer. The combination therapy mainly comprises combined application of L-selenomethionine and an immune checkpoint inhibitor (especially an anti-PD1 antibody). The composition can effectively inhibit tumor growth and enhance the tumor killing ability of an immune system. By reducing the number of tumor infiltration neutrophils and weakening the immunosuppression function of the neutrophils, the L-selenomethionine significantly improves the anti-tumor immune response. The invention provides a safe and effective treatment choice, the curative effect of the immune checkpoint inhibitor is remarkably improved, and a new treatment hope is brought to patients.