90 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 belongs to the field of biological catalytic materials, particularly relates to a sound-sensitive agent based on a metal-pyridine coordination structure as well as a preparation method and application of the sound-sensitive agent, and more particularly relates to a sound-sensitive agent doped with second metal and based on the metal-pyridine coordination structure. Compared with other most reported sound-sensitive agents based on micromolecules, the sound-sensitive agent based on the metal-pyridine coordination structure and the doped second metal and based on the metal-pyridine coordination structure, especially the latter, has higher ultrasonic mediated < 1 > O2 generation activity; in addition, the effects of relieving oxygen deficit, promoting polarization of macrophages to M1 and enhancing immunotherapy are achieved, and therefore the tumor microenvironment of immunosuppression is reversed. When the sonosensitizer provided by the invention is used in combination with a PD-L1 antibody, satisfactory sonodynamic triggered synchronous immune activation is realized, and original and distant metastatic tumors are eradicated impressively.

The invention relates to a multifunctional silica plastid integrating chemotherapy, immunotherapy and gas therapy, and relates to a preparation method of the multifunctional silica plastid and application of the multifunctional silica plastid in tumor diagnosis and treatment. The schematic diagram is as shown in the figure, the membrane components comprise conventional phospholipid and complex lipid, a chemotherapeutic drug doxorubicin (DOX) entrapped on a hydrophilic core and Fe3 (CO) 12 entrapped on a hydrophobic core, and the chemotherapeutic drug can be adjusted according to needs and is suitable for broad-spectrum tumor treatment. The drug-loaded silica plastid can generate part of carbon monoxide in a tumor high-concentration hydrogen peroxide (H2O2) environment and release internally-loaded chemotherapeutic drugs. Under the action of ultrasound (US), the multifunctional silicon plastid can realize fixed-point release of chemotherapeutic drugs DOX and carbon monoxide at a tumor site, the enrichment and uptake of the drugs at the tumor site are greatly improved, in addition, the system is combined with the alphaPD-L1 antibody, the immunosuppressive PD-L1 / PD-1 axis can be blocked, T cells are recruited to attack tumors, meanwhile, the immunosuppressive regulatory T cells (Tregs) are reduced, and the tumor treatment effect is improved. The tumor inhibition can be enhanced; the pulmonary metastasis can be obviously reduced.

The present disclosure provides vaccine compositions comprising at least one adjuvant and at least one therapeutic factor. The disclosure also provides methods of reducing an immune suppressor cell population in a mammal, methods of argumenting an immune response in a mammal, and methods of treating a diseases in a mammal utilizing the vaccine compositions.

To provide treatment of cancers with GM-CSF antagonists.SOLUTION: The present invention provides, among other things, a method of treating cancer comprising administering a GM-CSF antagonist to a patient in need of treatment, where the administration of the GM-CSF antagonist results in inhibition of an immunosuppressive activity of myeloid-derived suppressor cells (MDSCs). The present invention also provides, among other things, a method of inhibiting immunosuppressive activity of myeloid-derived suppressor cells (MDSCs) in a patient suffering from cancer, comprising administering a GM-CSF antagonist to the patient.SELECTED DRAWING: None

There is provided herein compound of formula (I) as defined in Formula (I), wherein Ra, Rb, Rc, A and p have meanings given in the description, and pharmaceutically-acceptable salts and solvates thereof, which compounds are useful in the treatment of diseases in which pan-immunoproteasome inhibition is desired or required, and particularly in the treatment of cancer.

The invention provides an anti-TIGIT antibody and IL-12 fusion protein and application thereof, and specifically, the fusion protein comprises a first binding region having TIGIT binding activity, a second binding region having TIGIT binding activity, and a third binding region having TIGIT binding activity; and a second binding region, the second binding region having an IL-12 receptor binding activity. The fusion protein can be effectively combined with TIGIT and IL-12 receptor protein molecules, the anti-TIGIT antibody relieves an immunosuppressive signal of TIGIT, meanwhile, IL-12 can promote proliferation and maintenance of immune cells and enhance the anti-tumor immune function, and the fusion protein can effectively treat and / or prevent cancers and has good clinical application value.

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 invention belongs to the technical field of experimental animals, and particularly relates to a machine learning transcriptome annotation-based large language model construction method, which comprises the following steps of: collecting culture data of a transcriptome annotation target disease sample; acquiring orthotopic transplantation animal data of the M transplanted orthotopic transplantation animals in the first transplanted time period; analyzing according to culture data of the transcriptome annotation target disease sample, orthotopic transplantation animal data of the M transplanted orthotopic transplantation animals and first transcriptome annotation target disease differentiation parameters, and respectively selecting complication immunosuppression transcriptome annotation target diseases from the M transplanted orthotopic transplantation animals, obtaining immune deep culture model data; and analyzing the cell activity of the to-be-transplanted animal by utilizing the deep model, and after the cell activity meets a first condition, selecting a transplantation position of the to-be-transplanted animal, so as to realize the construction of the orthotopic transplantation animal model of the transcriptome annotation target disease cell by utilizing a stereotactic technology.

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.

A vaccine for use in the prophylaxis and / or treatment of a diseaseThe present invention relates to an adenoviral vector capable of encoding a virus-like particle (VLP), said VLP displaying an inactive immune-suppressive domain (ISD). The vaccine of the invention shows an improved immune response from either of both of the response pathways initiated by CD4 T cells or CD8 T cells.

Provided herein are methods of measuring effects of immune suppression in a subject, the method comprising (a) quantifying a number of immune cells in a biological sample of the subject: (b) determining an expression level of a protein from the biological sample; and (c) analyzing the number of immune cells and the expression level of the protein, thereby measuring the effects of immune suppression in the subject.

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.

Soluble TREML1 is involved in many inflammatory diseases and plays an important role in immune suppression. Soluble TREML1 can bind the l-domain of CD11b 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 TREML14 induced immune suppression. Anti-TREML1 antibodies provide a novel and potential therapy for these disease conditions such as cancer.

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.

In certain aspects, the subject matter disclosed herein relates to high affinity monoclonal antibodies against LILRB4 and / or LILRB2 and their use in inhibiting myeloid-dependent, immune-suppressive signals and in cancer treatment. In certain aspects, the subject matter disclosed herein relates to bispecific molecules binding LILRB4 and LILRB2.

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.

The invention discloses an application of sodium cromoglycate in preparation of a pharmaceutical composition for promoting immunotherapy of breast cancer, and belongs to the technical field of tumor therapy, and the breast cancer is breast cancer with immunotherapy failure or immunotherapy drug-resistant breast cancer. The invention provides an application of sensitizing an immunotherapy drug in treatment of breast cancer by inducing antigen presenting related functional molecules on antigen presenting mast cells to be up-regulated by using sodium cromoglycate, remarkably enhancing antigen presenting mast cell mediated T cell anti-tumor immunity and inhibiting tumor growth resistant to immunotherapy. The sensitization immunotherapy curative effect of a mouse experiment shows that the sodium cromoglycate combined immunotherapy inhibits the growth of mouse breast tumor resistant to immunotherapy, and the prospective II-stage clinical test proves that the immunotherapy combined sodium cromoglycate has the curative effect and safety on a patient suffering from the triple negative breast cancer resistant to immunotherapy, and the immunotherapy combined sodium cromoglycate can be used for treating the triple negative breast cancer resistant to immunotherapy. The preset main curative effect end point is reached, and the adverse reaction is controllable.

The disclosure provides, in various aspects, methods of treating cancer in a subject in need of treatment therefor, comprising administering to the subject a therapeutically effective amount of an osteoprotegerin inhibitor, wherein the osteoprotegerin inhibitor inhibits osteoprotegerin binding to TRAIL. In further aspects, the disclosure provides methods of achieving a therapeutic outcome in a subject in need of treatment, wherein the method comprises the administration to the subject of a treatment which inhibits OPG-mediated suppression of tumor immunity.

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 present disclosure provides immune cell binding polypeptides (ICBPs) that include a binding moiety that can bind to ILT2 and / or ILT4 polypeptides, at least one immunoinhibitory polypeptide, and a scaffold polypeptide. The ICBPs are useful for inducing immunological tolerance. The present disclosure provides methods of inducing immunological tolerance.

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.