48results about How to "Improve the effect of immunotherapy" patented technology

The invention discloses a hydrophobic-modified polyethyleneimine and application thereof as a protein carrier. The structural general formula of the hydrophobic-modified polyethyleneimine is disclosed in the specification, wherein n is any natural number ranging from 5 to 20, and X is Cl, Br or I. The hydrophobic-modified polyethyleneimine can be compounded with protein to form stable nanoparticles, and thus, can be used as a protein carrier. Compared with the prior art, the hydrophobic-modified polyethyleneimine disclosed by the invention has strong protein binding force, can carry antigen protein, can be recognized by antigen presenting cells, and can initiate immunoreaction; and meanwhile, the hydrophobic-modified polyethyleneimine enhances the antigen cross-presentation effect, obviously lowers the cytotoxicity, is beneficial to enhancing the immunotherapeutic effect, and is an excellent therapeutic tumor vaccine nano carrier system.

The invention provides an anthocyanidin composite tablet helping PD-1 monoclonal antibody immunotherapy for colon cancer and rectal cancer with a purpose of enhancing effects of D-1 monoclonal antibody immunotherapy for the colon cancer and rectal cancer. The tablet is prepared from such active constituents as dry powder of extracts of anthocyanidin, casein and dry powder of probiotics, wherein the dry powder of extracts of anthocyanidin mainly contains 3-30% (by mass fraction) of anthocyanidin, non-starch polysaccharides and oligosaccharide and combines with the casein to produce particles; the probiotics include lactobacillus rhamnosus, streptococcus thermophilus, lactobacillus acidophilus, fermented lactic acid bacteria and bifidobacterium. Concerning needs for treatment of the rectalcancer and the colon cancer, the tablet of the invention also uses an ethyl acrylate and methacrylic acid copolymer enteric coating. According to the formula of the tablet of the invention, cancers ofMC38 colon cancer mouse and CT26 colon cancer mouse significantly reduce compared with a contrast group solely taking a PD-1 therapy.

The invention belongs to the immunotherapy and discloses a fusion protein as well as a preparation method and application thereof. The fusion protein disclosed by the invention comprises a protein HSP70 and a protein fused with an extracellular domain protein FPR1. The extracellular domain protein FPR1 comprises multiple amino acid sequences, and the amino acid sequences of different fragments ofthe extracellular domain protein FPR1 are connected by flexible linker peptides. The fusion protein disclosed by the invention is simple in preparation, high in specificity and long in duration time,and the immunotherapy effect can be obviously enhanced.

The invention relates to a DC targeted nano vaccine applied to immunotherapy of liver cancer and a preparation method thereof, which are characterized in that mannose modified ethylene glycol chitosanis used as a carrier material, a liver cancer specific polypeptide antigen phosphatidylinositol proteoglycan-3144-152 peptide (GPC-3144-152, FVGEFFTDV) is an immunizing antigen, and the nano vaccineis prepared by electrostatic interaction. The nano vaccine can increase the antigen endocytosis quantity of dendritic cell (DC), protect antigen from rapid degradation and clearance, prolong the action time of antigen, and stimulate the body to produce an effective immune response. The raw materials of the nano vaccine are cheap and easily available, the preparation method is simple and easy to repeat, the large-scale processing and production are simple, the immunotherapy effect of liver cancer can be enhanced, and therefore, the DC targeted nano vaccine has good application prospects.

The present invention relates to a formulation comprising an inhibitor of NFAT activation for use in treating or preventing undesirable effects, more particularly undesirable effects occurring in conjunction with T cell-mediated therapies. The undesirable effects may be cytokine release syndrome (CRS) or symptoms associated with gastrointestinal (GI) inflammation, for example associated with inflammatory bowel diseases, such as ulcerative colitis, optionally caused by activated T cell activity. In addition to ameliorating undesirable effects, the invention is aimed at also maintaining the therapeutic effects of the T-cell mediated therapy.

The invention discloses a chemotherapy-immunotherapy combined drug and a preparation method and application thereof. A PTX micelle based on PEG-P (CL-DTC) is designed, and the technical effect of combination of the PTX micelle and vesicles (CPs-CDN) with asymmetric membrane structures of interferon-gene-carrying stimulating protein (STING) pathway agonist Cyclic Dinucleotide (CDN) in treatment of breast cancer (TNBC) is studied. The PTX micelle is simple in preparation method, small in particle size and high in drug loading capacity and has good stability and reduction responsiveness. Experiments show that after the PTX micelle is combined with the CPs-CDN, more BMDC maturation can be promoted, CD4<+> T and CD8<+> T cells in tumors and spleens are significantly increased, inhibitory Treg is reduced, tumor growth and lung metastasis are obviously inhibited, the lifetime of mice is prolonged, and the advantages of chemotherapy-immunotherapy are embodied.

The invention discloses a water-soluble IDO (dioxygenase) inhibitor cisplatin and a preparation method and application thereof. The water-soluble IDO inhibitor cisplatin medicine synthesized with the preparation method comprises a hydrophilic compound formed by the coordination of an IDO inhibitor, or the derivative of the IDO inhibitor and a platinum antitumor drug. Compared with other IDO inhibitors, the IDO inhibitor cisplatin prepared with the preparation method has good water solubility, and the problem of low solubility of the IDO inhibitor is solved. Meanwhile, the water-soluble IDO inhibitor cisplatin medicine keeps the activity of the IDO inhibitor, improves an immunosuppression environment, keeps the killing function of the platinum drug for tumor cells, accelerates the releasing of tumor antigens, and increases an immunotherapy effect to achieve a purpose of the collaborative treatment of tumors.

The invention discloses an application of RBPJ as a drug target in preparation of a drug for inhibiting T cell depletion. The RBPJ can be used as a drug target for preparing a drug for inhibiting T cell depletion; the invention discloses a T cell depletion inhibitor. The inhibitor is an inhibitor for inhibiting the expression quantity of RBPJ. According to the invention, the RBPJ gene capable of being used as a target for preparing the medicine for inhibiting T cell depletion is obtained through screening, and the inhibitor capable of inhibiting the gene expression is designed and synthesized,so that the T cell depletion is effectively inhibited, and the tumor immunotherapy effect is enhanced.

The invention discloses an application of gamma interferon induced lysosomal sulfydryl reductase GILT in enhancement of anti-tumor immune response. It is found that high expression of GILT can promote infiltration of T cells in breast cancer tissue. GILT is overexpressed in breast cancer cells, and the killing ability of T cells to the breast cancer cells can be enhanced. The GILT provided by the invention can effectively promote T cell mediated anti-tumor immune response, and the breast cancer immunotherapy effect can be improved by activating GILT expression.

The invention discloses a class of iodine radioisotope labeled benzyl phenyl ether derivatives, a preparation method, a pharmaceutical composition and application thereof, and specifically relates toa benzyl phenyl ether derivative represented by a general formula I, a pharmaceutical salt, a stereoisomer and a preparation method thereof, a composition containing one or more radioactive compounds,and application of the radioactive compounds as PD-L1 tracers in human or animal bodies in diagnosis and treatment of diseases related to PD-1 / PD-L1 signaling pathways, such as cancer, infectious diseases and autoimmune diseases.

The present invention provides an mRNA cancer vaccine encoding human GM-CSF fused to multiple tandem epitopes. pVec-GM-CSF-hTes encoding human GM-CSF fused to three tandem hTERT epitopes, pVec-GMKE encoding human GM-CSF fused to three tandem epitopes respectively from MUC1, Kras and EGFR, pVec-hIL-12 encoding human interleukin-12 are respectively constructed, and used as templates for generating the corresponding in vitro transcribed mRNAs, which are mixed together as an mRNA cancer vaccine. This mRNA cancer vaccine contains human GM-CSF used as an immune adjuvant, multiple tandem epitopes constituting as multi-epitope cancer antigens and hIL-12 used to enhance the immunotherapeutic effects.

The invention discloses a cell culture method for improving DC-CIK (dendritic cell-cytokine-induced killer) cell killing ability. The cell culture method includes subjecting cultured DCs and CIKs to mixed culture in mixed culture liquid, wherein stimulating peptides shown in SEQ ID NO.1 are added into the mixed culture liquid and used for mixed culture of the DCs and the CIKs so as to stimulate to form DC-CIK cells. By changing the component of a culture system, the cell culture method changes the inhibiting effect between the DCs and the CIKs into the stimulating effect, so that the ability of the DC-CIK cells to kill target cells after co-culture can be improved, and improvement in immunological therapy effects is benefited.

The invention belongs to the technical field of medicines, particularly relates to A2A-targeting benzimidazopyrazine-3-formamide and a tumor immune function thereof, and discloses a subtype selective adenosine A2A receptor antagonist, namely a 1-amino-N-(pyridine-2-yl methyl) benzo [4, 5] imidazopyrazine-3-formamide small molecule compound, of which the structure is shown as a formula (I). Researches find that the small molecule compound can specifically target A2AR, inhibit cAMP accumulation, promote release of immune cell cytokines, enhance killing of immune cells on tumor cells in co-culture and enhance the tumor immunotherapy effect. The polypeptide shows an obvious tumor immunoenhancement effect in molecular level, cellular level and cancer mouse models, and is expected to be applied to tumor immunotherapy.

The invention discloses an application of a catalase-entrapped liposome connected with a PD-L1 antibody in preparation of a tumor treatment drug. The liposome is a multifunctional immune liposome which takes soyabean lecithin and cholesterol as skeletons, encapsulates catalase and is connected with aPDL1 on the surface. The liposome is prepared by a film dispersion / post-insertion method, wherein the catalase is entrapped in the liposome; the aPDL1 is an aPDL1 guide compound synthesized by reaction, and is inserted into a liposome phospholipid bilayer; and the surface of the liposome is also connected with a hydrazone bond. The liposome is of a spherical structure, the particle size of the liposome is 118.2 + / -1.763 nm, and the polydispersity index of the liposome is 0.223 + / -0.007; and theencapsulation efficiency of catalase is 30-36%. The drug obtained by the invention can effectively relieve hypoxia in a tumor region and block a tumor inhibitory signal path (PD-1 / PD-L1), has a goodtreatment effect on melanoma, and has a wide research prospect in the aspect of tumor immunotherapy.

The invention relates to a specific antibody delivery platform and a preparation method and application thereof. The preparation method of the specific antibody delivery platform comprises the steps that NK cells serve as target spots, the surfaces of ferroferric oxide nanoparticles are modified, and the ferroferric oxide nanoparticles and the antibody for specifically recognizing the NK cells are combined through chemical bonding. According to the specific delivery platform, the antibody and the particles are combined more stably in a chemical bonding mode, the NK cells can be specifically recognized and combined, and migration of the NK cells can be further promoted under the action of a magnetic field, so that enrichment of the NK cells at tumor sites can be rapidly and efficiently achieved, and the immunotherapy effect can be obviously improved. Therefore, the platform has a wide application prospect in medical detection, blood screening and targeted drug preparation.

The invention relates to a biomarker for predicting tumor immunotherapy response. Researches find that the expression level of THBS2 in lung cancer tumors is related to the clinical immunotherapy reaction effect; THBS2 can inhibit T cell proliferation of a non-small cell lung cancer patient. THBS2 is related to the expression of immune escape molecules; THBS2 is related to CD8+T and CD19+B cell infiltration reduction in lung adenocarcinoma tumors; THBS2 is derived from a partial subset of cancer-associated fibroblasts (CAF) in a tumor microenvironment, and the partial subset is different from a subset defined by a classical CAF marker. Based on the research results, the invention provides application of a reagent for detecting the expression quantity of the marker THBS2 in preparation of a product for evaluating the response of malignant tumors to immunotherapy and application of THBS2 positive expression CAF as a potential target in overcoming immunotherapy drug resistance.

The invention provides an antagonistic peptide, a copolymer thereof, a nano-assembly as well as preparation methods and applications of the antagonistic peptide, the copolymer and the nano-assembly. The antagonistic peptide is a PD-L1 antagonistic peptide, is named M-APP, and has a structure shown in the specification. The M-APP is used as a raw material to prepare the copolymer IR780-M-APP with aclear structure, the copolymer IR780-M-APP can be self-assembled to form the nano-assembly, so that the problem of poor immunogenicity in immunotherapy is solved, and the utilization rate of the immune antagonistic peptide is improved; and through photodynamic therapy, the problem of poor water solubility of IR780 can be solved, the effect of phototherapy is improved, and the efficacy of immunotherapy is enhanced.

The invention provides a preparing method of a 1-MT-carboxymethyl chitosan drug. According to the preparing method, 1-methyl-DL-tryptophan serves as a raw material, firstly, BOC amino protection is conducted on 1-methyl-DL-tryptophan through di-tert-butyl dicarbonate ester, then 1-methyl-DL-tryptophan and carboxymethyl chitosan are subjected to an amide reaction, through water desorption of BOC groups, the BOS groups are removed, and then the 1-MT-carboxymethyl chitosan drug is obtained. The prepared 1-MT-carboxymethyl chitosan drug inhibits the activity of indoleamine 2,3-dioxygenase with thetumor immune escape function, thus immune escape of indoleamine 2,3-dioxygenase is avoided, and then the immunotherapy effect of the antitumor drug is improved.

The invention relates to the technical field of medicine, in particular to an enzyme-sensitive nano system targeting T cells and its preparation method and application. The enzyme-sensitive nanosystem targeting T cells provided by the present invention is based on a polypeptide carrier and can be loaded with hydrophobic therapeutic drugs. The end of the polypeptide is modified with a functional group and can be connected with a functional antibody targeting T cells. The polypeptide carrier includes a hydrophobic segment and a hydrophilic segment, which can self-assemble into micelles and have good drug-loading capacity; the end of the polypeptide introduces a maleimide group, which can be connected to functional antibodies such as antibodies targeting T cell surface proteins. substance. The present invention provides a new nano system for drug delivery, which can target T cells to deliver hydrophobic therapeutic drugs and antibody drugs, restore the function of immune cells, thereby promoting the apoptosis of prostate cancer cells, and is a new method of immunotherapy for prostate cancer. An efficient and low toxicity nanoscale delivery system.

The invention discloses magnetotactic immune cells. The magnetotactic immune cells comprise immune cells and magnetic nanoparticles taken into the immune cells. The magnetotactic immune cells disclosed by the invention can be effectively enriched in a tumor site to improve targeting of the cell immunotherapy.

The invention discloses application of IFN-alpha and HDACi to preparation of a medicine for treating tumor, and belongs to the technical field of biotechnology and medical technology. Application of the IFN-alpha and HDACi disclosed by the invention to preparation of the medicine for treating tumor is disclosed. By using HDACi inhibitor, tumor cancers are treated, and then IFN-alpha is added, andverification shows that the inhibitor for epigenetic modification can further activate interferon-related signaling pathway STAT and expression of interferon responsive genes, recruits and activates parts, reaching the tumors, of immune cell subpopulations while inflammatory reaction of the inhibitor is enhanced, and the immunotherapy effect of the tumors is improved.

The invention discloses a jujube processed product capable of improving colon cancer and / or rectal cancer immunotherapy effects and a using method thereof. The invention claims the protection of an application of the jujube processed product in the preparation of products for intensive immunotherapy of colon cancer and / or rectal cancer. The invention also claims the protection of an application ofthe jujube processed product in the preparation of products capable of improving the antitumor effects of PD-1 / PD-L1. The invention also claims the protection of an application of the jujube processed product in combination with a PD-1 / PD-L1 inhibitor in the preparation of products capable of improving the anti-tumor effects of PD-1 / PD-L1. By using the jujube processed product and the using method provided by the invention, the tumor of MC38 colon cancer mice can be significantly reduced compared with the control group treated with PD-L1 alone.

The invention relates to the technical field of genetic engineering, in particular to a chimeric antigen receptor nano-antibody exosome. The exosome is CAR-NB-exo, and the surface of the exosome specifically comprises three antibodies, a first antibody is a CD3 antibody, a second antibody is a CD33 antibody, and a third antibody is a PD-L1 nano-antibody. The invention also discloses a purification method of the chimeric antigen receptor nano-antibody exosome. The purification method comprises the following steps: step 1, collecting a culture medium of Expi293 cells transfected by an expression construct on the third and sixth days after transfection; and step 2, separating the CAR-NB-exo through differential speed centrifugation and ultra-speed centrifugation. Compared with the prior art, the exosome has the beneficial effects that the generated dual targeting T cells CD3 and CD33 can be combined with the surfaces of the T cells and cancer cells, and besides, the PD-L1 nano antibody can block the combination of the cancer cells and PD-1 receptors on the surfaces of T lymphocytes, so that the effect of immunotherapy can be greatly improved.

The invention discloses heterojunction functionalized chlorella. The heterojunction functionalized chlorella consists of chlorella cells and black phosphorus nanosheets which are loaded on the surfaces of the chlorella cells, are used for modifying polyaspartic acid and are chelated with iron ions. The black phosphorus nanosheet and an original photosynthetic system in chlorella cells are coupled to construct a type II heterojunction, the oxygen production capacity of chlorella photosynthesis and the photodynamic < 1 > O2 production capacity of the black phosphorus nanosheet are synchronously and synergistically enhanced, the tumor hypoxic microenvironment is relieved, and the curative effect is enhanced; cGF generated by chlorella cells causes activation of an immune system, promotes antigen recognition, presentation and immune response of the body immune system and enhances the immunotherapy effect, and Fe < 3 + > released by heterojunction functionalized chlorella enters tumor cells, can consume GSH and is reduced into Fe < 2 + >, so that the oxidation resistance of the tumor cells is weakened, and the immunotherapy effect is enhanced. The Fe < 2 + >-mediated Fenton reaction increases the curative effect of chemodynamic therapy on tumors.

The invention discloses a DNA network hydrogel, a preparation method and a composition thereof, the network hydrogel comprises a network hydrogel carrier having a network structure formed by a DNA chain; and the HhaI (at) TGMS nano particles are loaded on the network hydrogel carrier. According to the invention, controllability of DNA network degradation and T cell release is endowed, so that blocking of immune checkpoints on cell surfaces and responsive release of tumor T lymphocytes are realized, and the nano-carrier is successfully applied to tumor immunotherapy and plays a remarkable immune curative effect in a melanoma mouse model.

The invention discloses a polyethyleneimine derivative and application thereof in preparation of an immunologic adjuvant, and belongs to the technical field of biological medicine. According to the invention, aryl aldehyde is modified on polyethyleneimine through Schiff alkali reaction to prepare a polyethyleneimine derivative, and the polyethyleneimine derivative is further prepared into the functional nano adjuvant. The nano adjuvant can effectively promote activation of cytotoxic T cells by promoting maturation of DC cells and phagocytosis of antigens; after being combined with a chemical drug, the compound can enhance the immune efficacy of the chemical drug and relieve the systemic toxicity of the chemical drug, so that tumor killing is effectively realized.

The invention relates to a preparation method of an antigen and adjuvant co-delivery nano-vaccine applied to liver cancer immunotherapy. The preparation method comprises the steps as follows: step 1,mixing a GPC3127-136 aqueous solution and a polyethylenimine (PEI) aqueous solution to obtain GPC3127-136 and PEI mixed solution, and mixing a sodium alginate aqueous solution and a CpG aqueous solution to obtain a sodium alginate and CpG mixed solution; and step 2, dropwise adding the sodium alginate and CpG mixed solution to the GPC3127-136 and PEI mixed solution under the stirring condition, and performing stirring continuously to obtain the antigen and adjuvant co-delivery nano-vaccine applied to liver cancer immunotherapy.

The invention relates to a composite liposome, a preparation method and application thereof. The composite liposome comprises the following components: 1) an immunomodulator-phospholipid conjugate; 2) a PEGylated photosensitive molecule; 3) a tumor treatment drug; and 4) phospholipid, in the composite liposome, the immunomodulator-phospholipid conjugate 1), the PEGylated photosensitive molecule 2) and the phospholipid 4) form a liposome, and the tumor treatment drug 3) is loaded in a physical entrapment form. The compound liposome can selectively target a tumor area, photosensitive molecules in the liposome can be activated to generate heat through local illumination on the tumor area, the permeability of the liposome is changed while tumor cells are killed, and release of loaded drugs in the liposome is promoted.

The invention discloses a hydrophobic-modified polyethyleneimine and application thereof as a protein carrier. The structural general formula of the hydrophobic-modified polyethyleneimine is disclosed in the specification, wherein n is any natural number ranging from 5 to 20, and X is Cl, Br or I. The hydrophobic-modified polyethyleneimine can be compounded with protein to form stable nanoparticles, and thus, can be used as a protein carrier. Compared with the prior art, the hydrophobic-modified polyethyleneimine disclosed by the invention has strong protein binding force, can carry antigen protein, can be recognized by antigen presenting cells, and can initiate immunoreaction; and meanwhile, the hydrophobic-modified polyethyleneimine enhances the antigen cross-presentation effect, obviously lowers the cytotoxicity, is beneficial to enhancing the immunotherapeutic effect, and is an excellent therapeutic tumor vaccine nano carrier system.