61 results about "Immune Evasions" patented technology

Parvoviral capsid with incorporated Gly-Ala repeat region The present invention provides a nucleic acid construct comprising a nucleic acid sequence encoding a parvoviral VP1, VP2 and VP3 capsid proteins comprising an immuno evasion repeat sequence. In addition, the present invention provides a cell comprising such construct, a parvoviral virion comprising a capsid protein that comprises an immune evasion repeat sequence, use of that parvoviral virion in gene therapy and a pharmaceutical composition comprising such parvoviral virion.

It is now recognized that chronic inflammation is an important risk factor for the development of cancer. The proinflammatory cytokine IL-6 is implicated in cancer because it is important for the activation of STAT, a key regulator of cancer growth, survival, metastasis, immune evasion and angiogenesis. Increased IL-6 and Stat-3 exists in vitro in pancreatic cancer, malignant melanoma, papillary thyroid cancer, breast cancer, colon cancer, and prostate cancer cells with high basal expression of Toll-like receptor 3 (TLR3) and Wnt5a. IL6 / STAT3 activation, mediated by overexpressed TLR3 signaling, appears important in the tumor growth process, it may increase Wnt5a signaling, and be associated with increased cellular growth and migration. Using a novel inhibitor of pathologic TLR3 signaling (5-phenylmethimazole [C10]) we have demonstrated decreases in these markers plus suppression of cell growth and migration in human pancreatic cancer, malignant melanoma, papillary thyroid cancer, breast cancer, colon cancer, and prostate cancer cells.

The invention discloses a preparation method of a human skin stem cell factor nano-liposome-exosome complex. According to the method, the exosome and the liposome are compounded, and through the synergistic effect between the exosome and the nano-liposome coated with the cytokine, the obtained compound system has good biocompatibility and immune escape performance, is free of cytotoxicity, not prone to being degraded by macrophages, good in stability and capable of continuously playing a role in vivo.

The invention discloses an exosome-nucleic acid aptamer liposome composite drug carrier system which comprises an anti-tumor medicine, wherein the surface of the anti-tumor medicine is wrapped by nano-liposomes, a nucleic acid aptamer is connected with the surfaces of the nano-liposomes through chemical bonds to form a nucleic acid aptamer liposome on which the anti-tumor medicine is carried; thenucleic acid aptamer liposome on which the anti-tumor medicine is carried is compounded with exosome. The invention further discloses a preparation method and an application of the composite drug carrier system. The composite drug carrier system is good in targeting property, good in immune evasion property, free of cytotoxicity and not liable to be degraded by macrophage, can be applied to anti-tumor medicine chemotherapy of cancer patients, is capable of greatly improving the treatment effect of anti-tumor medicines, reducing the situations of chemotherapy effect degradation and disease reoccurrence caused by drug resistance, and alleviating the bottle neck problems of conventional chemotherapy of cancer patients, and has great application values and application prospects in intensifyingcancer treatment effects.

The present invention provides 5T4 tumour-associated antigen (TAA) for use in a method of immunotherapy of tumours. The invention also relates to a recombinant poxvirus vector from which at least one immune evasion gene has been deleted, which comprises a nucleic acid sequence encoding a 5T4 TAA and the use thereof in vaccinating against and in treating tumours.

This invention provides immunogenic compositions comprising two or three recombinant Herpes Simplex Virus (HSV) proteins selected from a gD protein, a gC protein and a gE protein; and methods of impeding immune evasion by HSV, inducing an anti-HSV immune response, and treating, suppressing, inhibiting, and / or reducing an incidence of an HSV infection or a symptom or manifestation thereof, comprising administration of a vaccine of the present invention.

This invention provides vaccines comprising two or more recombinant Herpes Simplex Virus (HSV) proteins selected from a gD protein, a gC protein and a gE protein; and methods of impeding immune evasion by HSV thereby vaccinating a subject against HSV and treating, suppressing, inhibiting, and / or reducing an incidence of an HSV infection or a symptom or manifestation thereof, comprising administration of a vaccine of the present invention.

The present invention provides a novel approach to the modulation of the immune response, directing it towards specific antigens, away from antigens against which no response is desired. The invention is based on the use of viral immune evasion proteins, such as UL49.5, which block antigen presentation to CD8+ T cells. The viral immune evasion proteins are used for: 1) the induction of tumor-specific or virus-specific immunity in cases where a conventional immune response is absent due to antigen processing defects; 2) the induction of empty MHC class I molecules at the cell surface that can be loaded with peptides of a desired specificity; 3) the inhibition of unwanted immune responses against transplanted tissues or organs, e.g. against islets of Langerhans in type 1 diabetes or allogeneic stem cells, or against self antigens in the case of autoimmunity.

The invention relates generally to the field of virology, and relates to the identification and characterization of the targets involved in the evasion strategy of viruses and to the use thereof in methods to identify anti-viral compounds. More in particular to identify compounds which are modulators of myosin light chain kinase (MLCK), a target within said entry and immune-evasion strategy. Other aspects of the invention are directed to anti-viral compounds identified using the models and methods of the present invention, as well as to the use thereof in treating viral infections, such as for example caused by the feline infectious peritonitis virus (FIPV), a coronavirus which belongs to an antigenic group which comprises in particular feline enteric coronavirus (FECV), canine coronavirus (CCV), swine transmissible gastroenteritis coronavirus (TGEV), porcine respiratory coronavirus (PRCV) and human coronavirus (HCV), and which induces, in a host-dependent manner, a range of symptoms which range from mild enteritis to the severe debilitating disease, and, in some cases, up to death. In a particular aspect the present invention provides the use of MLCK inhibitors for the treatment of feline infectious peritonitis (FIP).

The invention discloses a medicine or health food for preventing or / and treating the Alzheimer's disease by a thymus pathway. The medicine or health food for preventing or / and treating the Alzheimer'sdisease by the thymus pathway is characterized in that the thymus pathway is aging, atrophy of thymus, decline in the immune function and development of the Alzheimer's disease, and fresh eclipta juice, recovery of thymus, improvement of the immune function, and interrupt or reverse of the development of the Alzheimer's disease. The drug or the health food is taken from fresh eclipta juice, the eclipta polyphenols flavones content in the fresh eclipta juice is 5.00-30.00%, the content of thiophenes is 1.00-10.00%, and the content of wedelolactone is 0.5-10.00%. According to the medicine or health food for preventing or / and treating Alzheimer's disease by the thymus pathway, the persisten inflammatory reaction is terminated during the stage when the pathogen infects the nasal cavity, oralcavity, intestinal tract and liver, the central nervous system is entered along special channels, and the occurrence of the Alzheimer's disease is prevented; and / or / when evolving virus, or immune evasion modified toxin enters the central nervous system stage, the persistent neuritis response is terminated, the Alzheimer's disease pathological cascade reaction is interrupted, and the early-to-midAlzheimer's disease is treated.

The invention discloses a preparation method of a porcine TLR4 polyclonal antibody. According to the preparation method, recombinant TLR4 protein (antigen) and freund's adjuvant are emulsified, then an immune animal obtains polyclonal antibody serum, wherein the recombinant TLR4 protein has the amino acid sequence as indicated in the sequence table SEQ. ID. No. 1. It is shown through tests that the antibody prepared through the method is good in reactivity and specificity; due to the fact that a TLR4 gene is a member of a significant pattern recognition receptor Toll-like receptor family targeted to innate immune response, the porcine TLR4 polyclonal antibody can be applied to detection of the porcine TLR4 protein and related research; a good foundation is laid for researching the interaction mechanism between porcine bacterial and viral infection diseases and TLR4 and the virus immunity escape mechanism, and a new target is provided for developing new generation vaccine and medicine. Meanwhile, a prokaryotic expression vector constructed through the method is high in recombinant protein expression efficiency, and the separation and purification method is simple and easy to operate.

The invention discloses a preparation method of a hydrogel tumor vaccine, the hydrogel tumor vaccine prepared by the preparation method and application of the hydrogel tumor vaccine. The preparation method comprises the steps as follows: 1) tumor cell pretreatment: adding a hydrophobic drug to tumor cells serving as a carrier to obtain pretreated tumor cells; 2) preparation of a hydrogel carrier: dissolving polypeptides and inorganic alkali in a buffer solution, and after full dissolution, carrying out heating in a water bath at 30-90 DEG C for 5-50 min to prepare the hydrogel carrier; and 3) preparation of the hydrogel tumor vaccine: in a vortex state, slowly adding the hydrogel carrier prepared in the sep 2) to the pretreated tumor cells prepared in the step 1), performing uniform mixing, and leaving the mixture to stand to obtain the hydrogel tumor vaccine. The hydrogel tumor vaccine combines a tumor cell vaccine and the hydrophobic drug, and can inhibit immune evasion mechanisms while enhancing specific antigen presentation and efficiently inhibit tumor metastasis and recurrence.

The invention provides a hepatitis B virus e antigen immune evasion detection gene chip and a kit, belonging to the gene chip technique field of clinical detection, and comprising: a gene chip of a specific DNA probe which detects hepatitis B virus e antigen immune evasion and is fixed on a solid phase carrier as well as a matched reagent; the matched reagent includes a treating fluid for treating serum samples, an amplifying solution for amplifying and labeling the treated samples, a hybridization solution in hybridization reaction with a micro-array, a cleaning solution, an enzyme-labeled working solution and a detection liquid; and the matched reagent and the hepatitis B virus e antigen immune evasion detection gene chip are used jointly in the detection process of the serum samples. The chip and the kit can detect the hepatitis B virus e antigen immune evasion, and avoid the clinical hepatitis B virus e antigen leak detection, thereby being favorable for judging the infectivity and conditions after curing of hepatitis B patients.

No effective vaccine exists for the devastating parasitic disease of Schistosomiasis. The present invention focuses on Sm-p80, a functionally important antigen of Schistosoma mansoni that plays a pivotal role in the schistosome immune evasion process. When used in a novel vaccine formulation, Sm-p80 demonstrates consistent immunogenicity, protective potential, and antifecundity effects. Two novel DNA constructs were made for immunization purposes. Sm-p80 coding sequence was cloned into VR 1020. Additionally, Sm-p80 coding sequence was cloned into pcDNA3.1 with flanking CpG motifs on each end of the Sm-p80 sequence. When used in different vaccine formulations, both of the constructs demonstrate the superior antifecundity and anti-worm effects of Sm-p80, which has great potential as an important vaccine candidate for the reduction of the morbidity associated with schistosome infection.

This invention discloses recombinant hepatocarcinoma composite epitope antigen, and its preparation method and application in manufacturing hepatocarcinoma-specific immunotherapy drugs. The composite epitope antigen has transduction activity, and contains T cell epitopes of several tumor antigens. The composite epitope antigen is obtained by gene synthesis and molecular cloning, and has such advantages as high safety and stability, and reduced immune evasion. The composite epitope antigen has potential applications in specific immunotherapy of liver cancer.

The invention provides Streptococcus vaccine strains (e.g. S. equi which is causative of ‘strangles’) comprising the following modifications in their genomes: (i) attenuation of one or more essential biosynthetic genes, (ii) attenuation of one or more genes which encode a haemolytic toxin, or protein involved in the production thereof, plus preferably any one, two, or most preferably three of the following modifications: (iii) attenuation of one or more genes which encode a protein responsible for immune evasion (iv) modification of one or more genes such as to permit serological discrimination of the vaccine strain based on analysis of a protein encoded by said genes, and (v) attenuation of one or more genes which encode an enzyme responsible for recombination repair of the genome. The invention provides inter alia live attenuated vaccine strains which generate an immune response to multiple protective epitopes presented in a context resembling the live pathogen.

The invention belongs to the field of chemical medicine, and particularly relates to a small molecule compound having an IDO1 / TDO double target, wherein the general formula is defined in the specification. According to the present invention, the embodiment schemes prove that the small molecule compound can simultaneously inhibit two enzymes IDO1 and TDO so as to reduce the immune evasion of tumorcells, achieve self-cure of tumor diseases, achieve good medicinal potential and provides new potential choice for clinical medication; the preparation method has characteristics of simpleness, mild reaction condition, convenient operation, convenient control, low energy consumption, high yield and low cost, and is suitable for industrial production; and the prepared compound has advantages of high biological activity, strong selectivity to tumor cells, remarkable drug-like properties, and good application prospects in the pharmaceutical industry.

Provided is an enveloped viral vector comprising a viral particle surrounded by an envelope, wherein the viral particle comprises a heterologous transgene, and the envelope comprises a lipid bilayer and one or more immunosuppressive molecules, and methods for preparing and using same.

The invention discloses a polypeptide for inhibiting PD-L1 palmitoylation modification and expression and application of the polypeptide and relates to the technical field of biological pharmacy. Thepolypeptide is a fusion polypeptide of a cell-penetrating peptide and a PD-L1 palmitoylation-inhibiting polypeptide; the cell-penetrating peptide is a TAT protein transduction peptide; and the PD-L1 palmitoylation-inhibiting polypeptide is a PD-L1 protein-targeting targeting peptide. The polypeptide disclosed by the invention implements competitive inhibition on endogenous PD-L1 palmitoylation modification of tumor cells, induces PD-L1 proteins to be degraded and cleared by a lysosome and reduces the contents of PD-L1 on the surfaces of the tumor cells and in the cells at the same time. Compared with an anti-PD-L1 antibody, the polypeptide disclosed by the invention fundamentally lowers the content of the Pd-L1 in the tumor cells and is more beneficial to overcoming the immune escape function obtained by the tumor cells through expression of the Pd-L1.

Granulin-epithelin precursor (GEP), a pluripotent growth factor, is a hepatic oncofetal protein defining a cancer stem cell (CSC) population in liver cancer. The present invention provides the use of GEP inhibitors (including anti-GEP antibody) for inhibiting immune evasion by liver cancer cells and for eliminating liver cancer stem cells.

The invention relates to erythrocyte membrane coated magnetic nanoparticles as well as a preparation method and application thereof, particularly, the PEG-Fe3O4 prepared by a hydrothermal method is extruded and coated with targeted modified erythrocyte membrane fragments to prepare the nanoparticle erythrocyte membrane-PEG-Fe3O4 with immune evasion and sensitive magnetic responsiveness, the nanoparticle erythrocyte membrane-PEG-Fe3O4 can adsorb cancer cells sensitive to folic acid in target, and cancer cells can be conveniently killed by magnetic field control or photo-thermal stimulation. The erythrocyte membrane-PEG-Fe3O4 can be effectively adsorbed to a folic acid-sensitive cancer cell membrane in target and endowed with cancer magnetic responsiveness, which is beneficial to movement control by a magnetic field and killing by photo-thermal stimulation. Therefore, the erythrocyte membrane coated magnetic nanoparticles have potential application prospects in the aspects of targeting therapy and industrial popularization.

This disclosure provides to methods for treating Hodgkin lymphoma in a subject comprising nivolumab, a PD-1-blocking antibody, that inhibits tumor immune evasion in patients with relapsed or refractory Hodgkin's lymphoma.

The present invention provides 5T4 tumour-associated antigen (TAA) for use in a method of immunotherapy of tumours. The invention also relates to a recombinant poxvirus vector from which at least one immune evasion gene has been deleted, which comprises a nucleic acid sequence encoding a 5T4 TAA and the use thereof in vaccinating against and in treating tumours.

The present invention provides compositions for the prevention and treatment of genital herpes, comprising nucleoside modified m RNAs that encode herpes simplex virus (HSV) glycoproteins, including those involved in virus entry and immune evasion, and methods of use thereof.

No effective vaccine exists for the devastating parasitic disease of Schistosomiasis. The present invention focuses on Sm-p80, a functionally important antigen of Schistosoma mansoni that plays a pivotal role in the schistosome immune evasion process. When used in a novel vaccine formulation, Sm-p80 demonstrates consistent immunogenicity, protective potential, and antifecundity effects. Two novel DNA constructs were made for immunization purposes. Sm-p80 coding sequence was cloned into VR 1020. Additionally, Sm-p80 coding sequence was cloned into pcDNA3.1 with flanking CpG motifs on each end of the Sm-p80 sequence. When used in different vaccine formulations, both of the constructs demonstrate the superior antifecundity and anti-worm effects of Sm-p80, which has great potential as an important vaccine candidate for the reduction of the morbidity associated with schistosome infection.

The present invention relates to a method for ex vivo generating and expanding MHCII restricted CD4+ Foxp3+ regulatory T cells, and therapeutic uses thereof. The inventors here demonstrated the optimal conditions for inducing Foxp3 expression in naive CD3+ CD4+ TCRαβ+ MHCII restricted T following polyclonal or following antigen-specific activation. They also developed an experimental procedure to generate autologous CD8+ T cell lines functionally committed to lyse tumor-antigen specific FOXP3 expressing TCRαβ+ MHCII restricted T cells, pathogenic CD4+ T cells that favour tumor cell immune evasion. In particular, the present invention relates to a method for generating ex vivo MHCII restricted CD4+ Foxp3+ regulatory T cells having the following phenotype: CD3+ CD4+ Foxp3+.