46results about How to "Enhance anti-tumor immunity" patented technology

Provided is an IL-15 heterodimeric protein, such as an IL-15 / IL-15Rα heterodimeric protein. The IL-15 heterodimeric protein contains protein (I) and protein (II). Protein (I) is recombinantly produced by combining IL-15 or a variant thereof with a first Fc variant, and protein (II) is a second Fc variant, or recombinantly produced by combining IL-15Rα or a variant thereof with a second Fc variant. The first Fc variant and the second Fc variant are preferably linked via a “Knob-into-Hole” mode. Also provided are methods of using the IL-15 heterodimeric proteins to modulate an immune response. The provided IL-15 heterodimeric proteins have significant anti-tumor activity, better biological activity and prolonged in vivo half-life compared to the IL-15 molecule alone.

Disclosed are methods of making a genetically modified immune cell for modifying a tumor microenvironment (TME) and methods of modifying a tumor microenvironment (TME). In some embodiments, the method can include delivering a first vector to an immune cell, wherein the first vector comprises a nucleic acid encoding a protein that induces T-cell proliferation, promotes persistence and activation of endogenous or adoptively transferred NK or T cells and / or induces production of an interleukin, an interferon, a PD-1 checkpoint binding protein, HMGB1, MyD88, a cytokine or a chemokine. Methods of modulating the suppression of the immune response in a tumor microenvironment, minimizing the proliferation of tumor and suppressive cells, and increasing the efficiency of an anti-cancer therapy, anti-infection therapy, antibacterial therapy, anti-viral therapy, or anti-tumoral therapy are also provided.

The invention discloses a novel replicating oncolytic adenovirus capable of simultaneously inhibiting immune checkpoints of PD-L1 and TIGIT and application thereof. According to the novel replicatingoncolytic adenovirus capable of simultaneously inhibiting immune checkpoints of PD-L1 and TIGIT, a soluble fusion protein capable of simultaneously inhibiting immune checkpoints of PD-L1 and TIGIT andactivating immune costimulatory pathways is characterized in that both ends of the soluble fusion protein are a PD1 (programmed cell death protein 1) extracellular region for binding PD-L1 and a PVR(poliovirus receptor) extracellular region for binding TIGIT respectively, PD1 fragments and PVR fragments are connected through a linker sequence, and both ends of the soluble fusion protein can simultaneously inhibiting the immune checkpoints of PD-L1 and TIGIT after binding PD-L1 and TIGIT respectively. Experiments show that the novel replicating oncolytic adenovirus (ad5sPD1PVR) can significantly inhibit the immune checkpoints and activate antitumor immunity effects, achieve significant antitumor activity and accordingly have a good prospect and high values for developing antitumor drugs.

Monoclonal antibodies, in particular 33.28 and 31.1, and chimeric antibodies, in particular mouse / humans chimeric Chi #1 specific for glycoprotein antigens of colon carcinoma-associated antigens which are immunogenic in humans, are disclosed. Such antibodies, and fragments and derivatives thereof, are useful in immunodiagnosis and immunotherapy of human colon, breast, and ovarian cancer, and for purification of antigens which can serve as immunotherapeutic agents. Methods of detecting the colon carcinoma-associated antigen in a sample, and methods for treating subjects having colon, breast, and ovarian carcinomas are disclosed.

The present invention relates to methods and compositions for use in mediating an immunosuppressive reaction. The compositions of the invention comprise exosomes having immunosuppressive activity. Such exosomes may be derived from a variety of different cell types, including antigen presenting cells such as dendritic cells and macrophages. Prior to isolation of exosomes, the cells may be genetically engineered to express molecules capable of enhancing the immunosuppressive activity of said exosomes and / or may be exposed to one or more agents, such as cytokines or cytokine inhibitors, which are also capable of enhancing the immunosuppressive activity of exosomes. The present invention also relates to the use of such exosomes for the treatment of diseases and disorders associated with undesirable activation of the immune system. The present invention also includes exosomes isolated directly from serum that have been shown to be immunosuppressive.

Provided is an IL-15 heterodimeric protein, such as an IL-15 / IL-15Rα heterodimeric protein. The IL-15 heterodimeric protein contains protein (I) and protein (II). Protein (I) is recombinantly produced by combining IL-15 or a variant thereof with a first Fc variant, and protein (II) is a second Fc variant, or recombinantly produced by combining IL-15Rα or a variant thereof with a second Fc variant. The first Fc variant and the second Fc variant are preferably linked via a “Knob-into-Hole” mode. Also provided are methods of using the IL-15 heterodimeric proteins to modulate an immune response. The provided IL-15 heterodimeric proteins have significant anti-tumor activity, better biological activity and prolonged in vivo half-life compared to the IL-15 molecule alone.

The present invention relates to methods of using compounds that inhibit the enzymatic activity of soluble human CD39 to treat cancer, including but not limited to the treatment of cancers characterized by CD73 expressing cells.

The present disclosure provides agents for treating and / or preventing resistance of tumor cells to radiation therapy (RT), the use and relevant method thereof.

The present invention relates to adenoviral vectors, wherein the viral capsid has been coated with polypeptides, which are capable of stimulating a peptide-specific immune response in a subject and uses thereof. Furthermore, the present invention relates to methods of treating diseases, e.g. cancer, by adenoviral vectors which have been coated by polypeptides causing peptide-specific immune response. Also the present invention relates to a method of coating adenoviral vectors by specific peptides as well as to a method of identifying those peptides suitable for coating the capsid of an adenoviral vector.

Described herein are compositions a genetically modified comprising nucleic acids encoding a chimeric antigen receptor (CAR) and a checkpoint inhibitor and methods for using the compositions to treatcancer.

The invention discloses an extracting process of cordyceps sinensis mycelium polysaccharide of a composite preparation for preventing a tumor, and the method comprises the following steps of: boiling 100 g of mycelium powder obtained by concentrating a cordyceps sinensis fermentation extracting solution; heating a filtering solution to obtain a concentrated solution; collecting the concentrated solution in a water bath so as to be concentrated; packaging the concentrated solution into eight centrifugal tubes so as to be centrifuged to obtain a water-soluble cordyceps sinensis polysaccharide solution; collecting liquid supernatant in the solution and slowly adding the liquid supernatant into absolute ethyl alcohol which is 4 times as much as the volume of the liquid supernatant; standing to obtain alcohol sediment; centrifuging and collecting alcohol precipitated polysaccharide in each centrifugal tube into each centrifugal tube; washing the alcohol precipitated polysaccharide twice by use of ethanol and freezing and drying in vacuum and at a low temperature to obtain a rough cordyceps sinensis mycelium polysaccharide; dissolving the rough cordyceps sinensis mycelium polysaccharide into distilled water and re-treating by suitable amount of the ethanol to obtain sediment; and freezing and drying the sediment in vacuum and at the low temperature to obtain cordyceps sinensis mycelium polysaccharide powder. The extracting process disclosed by the invention is used for finely sieving components in the rough polysaccharide to sieve components for accelerating anti-tumor immune cells to be multiplied, so that the anti-tumor immune effect of an organism is enhanced.

The invention provides a method for preventing tumor-induced T cell aging and reversing immunosuppression capability of the tumor-induced T cell. A ligand of a TOLL like receptor 8 is provided to a cell; a TOLL like receptor 8 (TLR8) signal channel in a tumor cell is activated; the tumor-induced T cell aging is blocked up, so as to improve the antitumor immunity. The ligand of the TOLL like receptor 8 is characterized by being oligonucleotides and comprising adenine, guanine, a main chain connecting bond for connecting the guanine and nuclease resistance residue of adjacent nucleic acid bases (preferably a chemical bond is phosphorothioate); a nucleic acid synthesis sequence is 5'-AGG...GA-3'; G represents guanine; A represents adenine; G and G are modified by a dithio phosphate ester bond; the number of G may be 3 to10 in difference; an acid synthesis sequence of a common ligand Poly-G3 is 5'-AGGGA-3'. By injecting TLR8 ligand Poly-G3 into the tumor, the inhibitory effect of a CD8<+>T cell can be significantly enhanced.

The invention is concerned with a method of predicting response to a PD-1 axis inhibitor such as anti-PD-L1 antibody by determining the abundance of dendritic cells (DCs) in a tumor tissue sample. The abundance of DCs characterized by enhanced expressions of XCR1, IRF8, BATF3 and FLT3 predicts clinical response to the PD-L1 blockade treatment.

The invention belongs to the field of gene engineering and particularly relates to a preparation method and an application of HLA-A0201-restrictive anti-Sox2 specific CTL. In the preparation method, with a cationic liposome of a C-typed agglutinin receptor on a targeted dendritic cell as an antigen supporter, a tumor stem cell antigen Sox2 is coated. The dendritic cell is quickly matured in 72 h and meanwhile positive antigen intake efficiency and MHC-I approach antigen presentation efficiency of the dendritic cell are improved. The method, compared with a conventional method in which the matured dentritic cells are obtained in 7-8 days, is greatly reduced in best therapeutic time window of tumor patients, so that the method is beneficial to generation of the signal-inductive antigen-specific CTL by stimulating initial T cells with abundant matured dendritic cells. With combination of engineering cells and cell factors, the antigen-specific T cells and Tcm are amplified in a large scale, thereby producing the Tcm being stronger in killing capability and being higher in ratio and further improving the anti-tumor immunity effect. The method can be used for quickly and effectively preparing the tumor stem cell antigen-specific CTL and has great economic value and market prospect.

The present invention relates to a new class of TNFR agonist comprising multiple binding portions to two different parts of the same TNFR. The present invention also relates to methods of activating components of the immune system in a patient via the administration of a TNFR agonist according to the present invention as well as the use of such materials for further therapeutic and other purposes.

The invention provides a method for preventing tumor-induced T cell aging and reversing immunosuppression capability of the tumor-induced T cell. A ligand of a TOLL like receptor 8 is provided to a cell; a TOLL like receptor 8 (TLR8) signal channel in a tumor cell is activated; the tumor-induced T cell aging is blocked up, so as to improve the antitumor immunity. The ligand of the TOLL like receptor 8 is characterized by being oligonucleotides and comprising adenine, guanine, a main chain connecting bond for connecting the guanine and nuclease resistance residue of adjacent nucleic acid bases (preferably a chemical bond is phosphorothioate); a nucleic acid synthesis sequence is 5'-AGG...GA-3'; G represents guanine; A represents adenine; G and G are modified by a dithio phosphate ester bond; the number of G may be 3 to10 in difference; an acid synthesis sequence of a common ligand Poly-G3 is 5'-AGGGA-3'. By injecting TLR8 ligand Poly-G3 into the tumor, the inhibitory effect of a CD8<+>T cell can be significantly enhanced.

The invention belongs to the technical field of medicine and discloses a traditional Chinese medicine capable of resisting cancer by improving immunity. The traditional Chinese medicine is prepared from red date, folium cycas, herba sculellariae barbatae, herba hedyotis diffusae, ganoderma lucidum, ganoderma applanatum, phellinus igniarius, pine needle, phaeoporus obliquus, raw trogopterus dung, raw black ipomopea hederacea, raw cyperus rotundus, raw costus root, herba sculellariae barbatae, lucid ganoderma, radix panacis quinquefolii, panax ginseng, radix codonopsis, radix salviae miltiorrhizae, red paeony root, radix angelicae sinensis, radix chuanxiong, radix astragali, bulbus lilii, edible tulip, asparagus, phellinus igniarius, 190 to 210 g of propolis, radix sophorae flavescentis, oyster, kelp, herba taraxaci, nightshade, summer mushroom grass and rhizoma curcumae longae. The traditional Chinese medicine contains various kinds of alkaloid and saponin, can inhibit tumor cell proliferation, inhibit telomerase activity, induce tumor cell apoptosis, stop cell cycle progress, improve tumor immunity and inhibit cancerometastasis and the like, and can improve the integrated immunologic function of people, stimulate immunocyte activity and promote a human body to generate an antibody so as to fulfill the anti-cancer aim.

The invention relates to a traditional Chinese medicine composition for improving tumor microenvironment. The traditional Chinese medicine composition mainly comprises the following components in parts by weight: lucid ganoderma, astragalus membranaceus, rabdosia rubescens, radix paeoniae rubra and medlar. The invention further provides a preparation prepared from the traditional Chinese medicine composition and a preparation method of the traditional Chinese medicine composition. The traditional Chinese medicine composition is capable of effectively suppressing the proliferation of tumor cells and promoting the death of the tumor cells, is high in suppression efficiency and free and toxic and side effects, and has good functions in improving the symptoms, controlling the tumor expansion, improving the living quality of the patients and prolonging the lifetime of the patients.

The invention provides homogalacturonan, a compound as well as a preparation method and application. The invention provides a preparation method of homogalacturonan, which comprises the steps of 1, pretreating to obtain stable water-soluble pectin gel; 2, carrying out treatment by an alkaline hydrolysis-microwave method; 3, carrying out methoxyl removal treatment; and 4, refining with an ultrafiltration membrane. The invention also provides a compound applying the homogalacturonan as well as a preparation method and application. The compound disclosed by the invention has a good medical effect, and the preparation method is simple in process, high in yield and low in cost.

The invention discloses a method for inhibiting dimethylbenzanthracene-induced rat mammary cancer with fucoidan, which relates to the technical field of mammary cancer inhibition. Sixty SPF (Specific Pathogen Free ) grade female SD (Sprague-Dawley) rats are randomly divided into a blank control group, a model control group, a low-dose fucoidan intervention group and a high-dose fucoidan intervention group according to body weights, fifteen rats in each group, the rats are killed after sixteen weeks, the incubation period and tumor inhibition rate of the mammary cancer of each group of rats are calculated, and thymus indexes, spleen indexes and the like are calculated. ELISA (enzyme-linked immunosorbent assay) is adopted to assay the levels of interleukins IL-6, IL-10 and IL-12, interferon-Gamma and transforming growth factor-Beta in serum, and a flow cytometer is utilized to assay the activity of NK (natural killer) cells in the peripheral blood of the rats and the cell percentage of the T-lymphocytes subset. The method has the following advantages that the method can regulate the immunity of rats, enhance antitumor immunity and relieve the immunosuppression of tumors, and the regulation of the activity of immune cells by fucoidan is one of the mechanisms of fucoidan in inhibiting the occurrence of mammary cancer.

The present invention discloses an anti-CD3 and anti-EpCAM bispecific antibody and an application thereof in treating lung cancer. The provided anti-CD3 and anti-EpCAM bispecific antibody is obtainedby connecting an anti-CD3 single-chain antibody and an anti-EpCAM single-chain antibody. The targeting and specific anti-CD3 and anti-EpCAM bispecific antibody is used as a bridge for binding of activated T cells and tumor cells to enhance an anti-tumor effect of effector T cells and body tumor immune response. Provided anti-CD3 and anti-EpCAM bispecific antibody molecular fragments can be constructed in vitro. The anti-CD3 single-chain antibody and the anti-Ep-CAM single-chain antibody are connected through a specific linker that does not affect action sites, and the anti-CD3 and anti-EpCAM bispecific antibody is high in binding sensitivity and large in affinity, and can bind two antigen epitopes simultaneously.

The invention provides a pharmaceutical composition for treating tumor and process for preparation, wherein the composition is prepared from gen-seng, Chinese blistering beetle or their extracts or their active constituents. The composition can improve the body's immunity function and suppress tumor cells directly.

The invention is directed to cancer immunotherapy. The invention is specifically directed to the induction of innate or adaptive antitumor immunity initiated by the administration of targeted IL-12 molecules preferably in conjunction with IL-2 and / or IL-7 to a cancer patient, who suffers from cancer of the muscle, bone, nerves, cartilage, tendons, blood vessels, etc., preferably from sarcoma. The invention is specifically related to the use of IL-12 in form of the specific immunoglobulin cytokine fusion protein called NHS-IL12, preferably in combination with a form of IL-2 and / or IL-7 exhibiting prolonged pharmacokinetics for the treatment of said cancer diseases.

The invention provides a traditional Chinese medicine preparation for improving the immunity of malignant tumor patients. The traditional Chinese medicine preparation comprises raw materials of saururus chinensis, aleppo avens, radix pseudostellariae, salvia miltiorrhiza, eclipta prostrate, semen euryales, dendrobe, rubus parvifolius, schisandra propinqua, roots of oriental paperbush, peperomia blanda, arundina graminifolia, hypericum sampsonii hance, acanthopanax roots, adenophora tetraphylla, herba epimedii, morinda officinalis, leaves of paniculate microcos, mulberry and vine of multiflower knotweed. Due to the adoption of the traditional Chinese medicine preparation, the anti-tumor immunity of the patients can be improved, a tumor can be prevented from reoccurrence or migration, and the traditional Chinese medicine preparation has a certain effect in prolonging the survival period with the tumor.

The present invention is directed to hybrid chimera antisense oligonucleotides including deoxyribonucleotide and 2′-deoxy-2′-fluoro-β-D-arabinonucleotide which binds to a Foxp3 mRNA, and to methods of use thereof. The methods include the use for reducing expression level of Foxp3 gene, increasing anti-tumor activity, and treating cancer in a subject.

The invention discloses a combined medicament used for treating the breast cancer. The combined medicament consists of an effective dose of BCG vaccine preparations, immunomodulators and pharmaceutically acceptable auxiliary materials. The combined medicament combines the BCG vaccine preparations and the immunomodulators, safety is good, in addition, expression of chemokine related genes and anti-tumor effect genes can be up-regulated, the expression of immunosuppression related genes can be down-regulated, an amount of tumor infiltrating lymphocytes is increased, and anti-tumor immunity is enhanced; and on an animal tumor model, growth of triple negative breast cancer tumors can be favorably restrained, and the combined medicament is better than any one independent medicine treatment method.

The invention relates to nucleic acid agents modulating the expression of SLAMF6 isoforms, compositions comprising same and methods for their use in immunomodulation. Specifically, provided are splice-switching oligonucleotides and constructs useful in cancer immunotherapy.

The invention provides a tumor vaccine and a preparation method thereof. The tumor vaccine comprises dendritic cells which block signal pathways of CD44 and CD11b molecules. The invention further provides a method for preparing the tumor vaccine. The method includes the following steps: (1) acquiring mononuclear cells from peripheral blood or umbilical cord blood of a mammal, inducing the mononuclear cells into mature dendritic cells or acquiring bone marrow hematopoietic precursor cells from bone marrow of the mammal, and inducing the mononuclear cells into mature dendritic cells; (2) blocking the signal pathways of the CD44 and CD11b molecules of the mature dendritic cells; and (3) collecting the dendritic cells blocking the signal pathways of the CD44 and CD11b molecules. The tumor vaccine has a good anti-tumor effect, a wide anti-tumor spectrum and good use safety.

The invention provides a tumor vaccine and a preparation method thereof. The tumor vaccine comprises dendritic cells blocking CD44 molecular signal channels. The invention also provides the method forpreparing the tumor vaccine. The method comprises the steps that 1) single karyocytes are obtained from the peripheral blood or umbilical cord blood of a mammal to be induced into the mature dendritic cells, or medullary hematopoiesis precursor cells are obtained from the bone marrow of the mammal to be induced into the mature dendritic cells; 2) the CD44 molecular signal channels of the mature dendritic cells are blocked; 3) the mature dendritic cells blocking the CD44 molecular signal channels are collected. The tumor vaccine has good tumor resistance, a wide anti-tumor spectrum and good use safety.

The invention provides a traditional Chinese medicine preparation for improving the immunity of malignant tumor patients. The traditional Chinese medicine preparation comprises raw materials of saururus chinensis, aleppo avens, radix pseudostellariae, salvia miltiorrhiza, eclipta prostrate, semen euryales, dendrobe, rubus parvifolius, schisandra propinqua, roots of oriental paperbush, peperomia blanda, arundina graminifolia, hypericum sampsonii hance, acanthopanax roots, adenophora tetraphylla, herba epimedii, morinda officinalis, leaves of paniculate microcos, mulberry and vine of multiflower knotweed. Due to the adoption of the traditional Chinese medicine preparation, the anti-tumor immunity of the patients can be improved, a tumor can be prevented from reoccurrence or migration, and the traditional Chinese medicine preparation has a certain effect in prolonging the survival period with the tumor.