35 results about "T cell immunity" patented technology

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus antigen epitope peptide and application thereof. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the amino acid sequence of the monkey pox virus antigen epitope peptide is shown as SEQ ID No.2. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

The invention discloses an RSV pre-F tripolymer protein combination and application thereof in preparation of bivalent RSV vaccines, and relates to the technical field of human vaccines. The vaccine is prepared by mixing an RSV-A subtype pre-F tripolymer protein and an RSV-B subtype pre-F tripolymer protein in equal mass, and matching with an aluminum hydroxide adjuvant with the concentration of 0.35 mg / 0.5 mL. A p27 fragment and a C-terminal esterification region of each of the two F proteins are deleted, the two F proteins are connected with F2 / F1 through GSGSGS, inter-chain disulfide bonds are introduced to S146C / N460C and A149C / Y458C sites respectively, intra-chain disulfide bonds are introduced to S155C / S290C sites respectively, and stable pre-F trimers are spontaneously assembled after secretion expression of CHO cells; the vaccine does not need to be freeze-dried, still keeps high purity and neutralizing epitope integrity after being stored at 37 DEG C for 28 days, can obviously induce neutralizing antibody and T cell immunity, and can be used for preventing various RSV-A / B infections.

The invention provides a polypeptide for activating cellular immunity in chronic hepatitis B and application of the polypeptide, and belongs to the technical field of biological medicine. A polypeptide library is designed and synthesized on the basis of a preS1 structural domain for coding HBV large HBsAg, a full-length core protein Core, a polymerase protein fragment rich in T cell epitopes and an mRNA-PreS1CPX holoantigen sequence (as shown in SEQ ID NO.1) of full-length X protein HBX, and peptide fragments capable of activating T cell immunity are screened by utilizing ELISPOT and flow cytometry. Experimental results show that the polypeptide sequences as shown in SEQ ID NO.2-15 can promote HBV antigen specific immune response by stimulating CD8 + T lymphocytes to secrete IFN-gamma, so that immune activation treatment of hepatitis B is realized.

To provide various compositions and methods useful for the treatment of pancreatic cancer, such as pancreatic ductal adenocarcinoma (PDAC), and methods for activating pancreatic tissue-specific anti-tumor T cell immunity.SOLUTION: In certain embodiments, such methods comprise administration of IL33. In certain embodiments, such methods comprise administration of PD-1 and / or PD - L1 inhibitors.SELECTED DRAWING: None

The application provides a bicyclic compound with a structure shown in formula (I) or a pharmaceutically acceptable salt, a stereoisomer or a prodrug molecule thereof, a pharmaceutical composition and application. The compound provided by the application can activate CD137, enhance the immune function of cytotoxic T lymphocytes (CTL), enhance the memory function of CD8+ T cells and CD4+ T cells, can make the polarization of CD4+ T cells tilt to a state beneficial to cellular immunity, and can promote the multimerization of CD137, so that T cell immunity can be effectively activated, the volume of a primary tumor can be effectively reduced, and the compound can be used for inhibiting and treating tumors.

The invention provides a tumor-associated fibroblast targeting nano adjuvant as well as a preparation method and application thereof, and belongs to the field of nano drugs. The nano adjuvant (named as PF9PEI and alpha PC NPs) provided by the invention is coupled with PEI25K modified by 3-perfluorobutyl-1, 2-epoxypropane by utilizing a PD-L2 targeting peptide nrirgenyryh, so that an efficient gene vector (PF9PEI) is formed, and is used for loading an alpha PD-L1-P2A-CD86 plasmid. According to the nano adjuvant, CAFs can be reprogrammed into engineered antigen presentation CAFs by expressing a costimulatory molecule CD86, so that T cell immunity of breast cancer specificity is activated, and T cell failure is retarded at the same time. Besides, the engineered CAFs generated by the nano adjuvant generate alphaPD-L1 locally, so that the immune escape mechanism of breast cancer cells is effectively blocked, and the immune surveillance function of T cells is recovered. After radiotherapy, by using the nano adjuvant for treatment, the generation of central memory T cells is promoted, the progress of the same solid tumor is inhibited, the tumor metastasis is eliminated, and the tumor recurrence is inhibited.

The invention provides agonistic anti-human VISTA antibodies and antibody fragments. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus CD8 < + > T cell epitope peptide, a composition and application of the monkey pox virus CD8 < + > T cell epitope peptide. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the monkey pox virus CD8 + T cell epitope peptide has an amino acid sequence as shown in SEQ ID No.1. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

The application discloses a kind of sea fish mycobacterium infection mouse model based on T cell immune state difference and its construction method and application.The method under unified infection condition (bacterial amount 1×10 4 CFU, temperature 25 DEG C, time 4 weeks), respectively, constructs the infection model of congenital T cell immune deficiency nude mouse and the thymus pentapeptide processing mouse model of acquired T cell immune regulation, by comparing and analyzing the infection phenotype and pathological changes under different immune states, for the mechanism of T cell immunity in non-tuberculous mycobacterium infection, screening immune regulation treatment drug provides standardized experimental model.

A lipid compound containing a heteroaromatic ring structure and use thereof. Provided is use of a compound in the preparation of a lipid carrier. The compound is a compound represented by formula I, a pharmaceutically acceptable salt thereof, or a conjugate thereof. A liposome drug prepared using the lipid compound has a good adjuvant effect, and can effectively activate T cell immunity.

The invention provides agonistic anti-human VISTA antibodies and antibody fragments. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

The invention provides a preparation method of a novel human / mouse cross-reactive anti-PD-1 candidate vaccine, and belongs to the technical field of candidate vaccine preparation. The candidate vaccine obtained by the preparation method can inhibit combination of PD-1 and PD-L1, can reactivate depleted T cells and break the tumor microenvironment of immunosuppression, and meanwhile, the epitope vaccine is combined with HBc VLPs to stimulate generation of strong T cell immunity, so that generation and development of tumor cells are inhibited in two aspects.

The invention discloses a method for enhancing the oxidative stress resistance of immune cells based on PRMT2 gene editing and application, and belongs to the technical fields of biology, biotechnology and immunotherapy. The invention further discloses a method for targeted knockout of protein arginine methyltransferase PRMT2 and application. The method can specifically, efficiently and stably silence expression of PRMT2. Experiments prove that the knockout of the PRMT2 can enhance the ROS removal capability of CD4 + T cells and CD8 + T cells and improve the oxidation resistance, so that the survival under oxidative stress and the generation of cell factors are enhanced; the killing activity of the CAR-T cells on tumor cells is effectively improved. The invention also discloses PRMT2 as an epigenetic inhibition factor of T cell immunity and a useful therapeutic target in infection and cancer immunotherapy. The method has a wide application prospect.

The application discloses a method for establishing a human alpha beta TCR and pMHC binding probability prediction model. The application designs a coding mode of TCR and pMHC amino acid sequences, trains a convolutional neural network through a machine learning method, and can predict the binding probability of TCR and pMHC. The prediction method has high prediction accuracy on unknown TCR, good generalization on single-chain TCR, double-chain TCR and single-double-chain mixed data, good prediction effect on CMV virus antigen-specific TCR, and is helpful for the research of T cell immunity.

This invention belongs to the interdisciplinary field of tumor immunotherapy and gene delivery, specifically relating to an aromatic hydrocarbon receptor blocking functional lipid nanoparticle, its preparation method, and its application. The ionizable lipid derived from the aromatic hydrocarbon receptor antagonist has the structure shown in formula (1): Formula (1), where x is an integer between 10 and 16, X is -N(Me)2 or -OH, and n = 0 or 1. This invention designs and synthesizes aromatic ionizable lipids that combine AHR antagonistic activity and nucleic acid delivery capability, constructing a functionalized LNP vector integrating AHR antagonism, nucleic acid delivery, and macrophage targeting. This vector can efficiently transfect macrophages in vivo and express CAR, while simultaneously blocking the AHR pathway in situ to reverse immunosuppression, enhancing antigen presentation, and activating T cell immunity. This fundamentally solves the core problem of the limited efficacy of existing CAR-M in vivo editing technology in solid tumors, especially gliomas.

Provided herein are methods for treating cancer by administering to a recipient mammal reprogrammed T cells. The reprogrammed T cells of the disclosure is produced by a method comprising administering to the donor mammal an effective amount of a composition comprising a plurality of glycopeptides as described herein. Also provided are methods of producing reprogrammed T cells. Also provided are methods for modulating dendritic cell or macrophage activity in a subject. The modulated dendritic cells or macrophages produced by such methods have improved antigen presentation and / or T cell priming activities.

The present invention relates to any one of a single epitope T cell antigen peptide, a multipotent T cell epitope peptide, and a DC cell loaded with a multipotent T cell epitope peptide for preventing and treating EBV infection. The DC cell loaded with a multipotent T cell epitope peptide can induce T cell immunity of the MHC-I pathway in vivo, rebuild the body's immune function, and stimulate the antiviral function of autologous CD8+CTL, and has both the preventive function of traditional vaccines and the therapeutic effect of traditional medicines. The single epitope T cell antigen peptide is selected from any one of MLRPVAPYR, GLSRMRERR, and RMRERRGRG or a combination thereof, and the multipotent T cell epitope peptide has a structure shown in formula I: wherein X is a basic amino acid, and Z is the single epitope T cell antigen peptide as described above.

The invention discloses a nanoparticle targeting HER2 breast cancer and application of the nanoparticle, a biological self-assembled helicobacter pylori ferritin nanoparticle (HPF) is used as a nano vaccine core, and a targeting dendritic cell WH peptide, an HER2 positive breast cancer target antigen HER2 extracellular domain and a T cell epitope immunogen AE37 peptide are covalently linked to the ferritin nanoparticle through a molecular glue system. The HER2 breast cancer targeting nanoparticles are obtained. The nanoparticles can be self-assembled, enhance immune response and simultaneously induce potent humoral immunity and T cell immunity, so that the anti-tumor effect is enhanced, and the nanoparticles can be applied to preparation of HER2 positive breast cancer vaccines.

The present application belongs to the technical field of immunotherapy, and particularly relates to a monkeypox virus antigen epitope peptide and application thereof. The present application aims to solve the technical problem that no T cell antigen epitope peptide for a monkeypox virus universal vaccine has been developed in the field of monkeypox virus. The technical scheme of the present application is a monkeypox virus antigen epitope peptide, the amino acid sequence of which is shown in SEQ ID No. 2. The antigen epitope peptide provided by the present application has strong immunogenicity and can induce antigen-specific CD8+ T cells; the antigen epitope peptide can be directly loaded into antigen presenting cells, can activate T cells, effectively induce T cell immunity, and can be used for research and development, preparation and drug research and development, and clinical treatment of a monkeypox virus universal vaccine.

The invention provides agonistic anti-human VISTA antibodies and antibody fragments. These agonist antibodies and antibody fragments may be used to potentiate or enhance or mimic VISTA's suppressive effects on T cell immunity and thereby suppress T cell immunity. These agonist antibodies and antibody fragments are especially useful in the treatment of autoimmunity, allergy, inflammatory conditions, GVHD, sepsis and transplant recipients. Screening assays for identifying these agonists are also provided.

The application discloses a kind of bioactive polyamino acid nanocomposites, preparation method and purposes, by condensation reaction synthesis hyaluronic acid-block-poly amphiphilic block copolymer, by hydrophobic, electrostatic, metal coordination etc. Interaction covers CD73 small molecule inhibitor APCP and PD1 / PD-L1 inhibitor S7911, preparation HA@APCP / S7911.HA@APCP / S7911 is enriched in tumor area by EPR effect, under the joint action of hyaluronidase and low pH in tumor area, realize the release of APCP and S7911 in tumor tissue.APCP is inhibited CD73 enzyme activity, restores the metabolism and activity of NK cell, starts NK cell immune response;S7911 is inhibited after release in tumor tissue PD-L1 and PD-1 binding, blocks immune checkpoint and starts T cell immunity, combined with radiotherapy to improve antitumor immune response, amplify the range of effective immune response, for promoting the combined effect of radioimmunotherapy provides a new way of thinking.

The invention discloses host-derived spermaceti capable of targeted enhancement of fish T cell immunity and application of spermaceti, and belongs to the technical field of microbial addition. According to the present invention, the cetobacter sobolifera strain is cetobacter sobolifera SH518, and the nucleotide sequence of the cetobacter sobolifera strain is represented by SEQ ID NO: 1; the invention also discloses an animal feed / probiotic feed. The animal feed / probiotic feed comprises a common feed and the spermaceti soxhlet; wherein no less than 107 CFU of the spermaceti is added into each gram of the common feed. According to the invention, the spermaceti soxhlet is added into the fish feed, so that the resistance of T cells of Nile tilapia to Edwardsiella fish killing infection is enhanced; the fish host-derived animal feed / probiotic feed provided by the invention is simple in preparation method, simple and convenient to operate, relatively low in cost and easy to popularize. The method has a wide application prospect.

The present invention provides a dengue tetravalent DNA vaccine and its application, belonging to the technical field of dengue vaccines. The nucleotide sequence of the dengue tetravalent DNA vaccine provided by the present invention is as shown in SEQ ID NO: 1. The dengue tetravalent DNA vaccine provided by the present invention is a DNA vaccine against four serotypes of DENV. After inoculating wild-type BALB / c mice with the DNA vaccine against four serotypes of DENV, specific IgG antibodies against four serotypes of dengue virus can be produced, and neutralizing antibodies with protective effects and antiviral specific T cell immunity can be induced.

The invention provides an ionizable cationic lipid as well as a preparation method and application thereof. The ionizable cationic lipid, auxiliary phospholipid, cholesterol and PEG lipid can be self-assembled to form lipid nanoparticles. Compared with a commercially available drug ionizable cationic lipid, the formed lipid nanoparticles can more efficiently deliver mRNA into animal bodies, protein can be more efficiently expressed in the bodies, and the safety index meets the commercially available medicinal requirements; the mRNA vaccine prepared based on the nanoparticles can induce high-level virus specific antibody, specific T cell immunity and memory B cell response reaction, and is very suitable for mRNA vaccine and drug development.

This invention belongs to the field of immunotherapy technology, specifically relating to a monkeypox virus CD8+ T cell antigenic epitope peptide, its composition, and its application. The technical problem this invention aims to solve is that, currently, no universal monkeypox virus vaccine using a T cell antigenic epitope peptide has been developed. The technical solution of this invention is a monkeypox virus CD8+ T cell antigenic epitope peptide, the amino acid sequence of which is shown in SEQ ID No. 1. The antigenic epitope peptide provided by this invention possesses strong immunogenicity and can induce antigen-specific CD8+ T cells; it can be directly loaded onto antigen-presenting cells, activating T cells and effectively inducing T cell immunity. It can be used for the development, preparation, drug development, and clinical treatment of a universal monkeypox virus vaccine.

The presently claimed and described technology provides vaccine compositions comprising at least two mutant-calreticulin (CALR)-peptides, wherein the at least two peptides have overlapping sequences and methods for administration of the vaccine compositions to induce or elicit an antitumor response or improve or enhance antitumor T cell immunity and methods of preventing, treating, reducing, or slowing progression or development of a hematological malignancy in a subject with a calreticulin mutation.

The present invention relates to the field of biomedical technologies, and discloses a recombinant herpes zoster vaccine based on gE / pORF7 dual-antigen nanocrystals and an intelligent phase-transition adjuvant, which includes dual-antigen nanocrystals formed by chemically bonding gE protein and pORF7 protein, wherein the gE protein forms the core, and the pORF7 protein is coupled to the surface of the core through dynamic covalent bonds; and an intelligent phase-transition adjuvant wrapped around the outer layer of the dual-antigen nanocrystals, and the adjuvant is composed of a thermosensitive polymer carrier and immunostimulatory molecules encapsulated therein, and the thermosensitive polymer carrier undergoes a phase transition within the range of 25-40°C. The vaccine of the present invention can simultaneously induce high-titer neutralizing antibodies and long-term T cell immunity, significantly improve the ability to clear the latent virus reservoir, and at the same time reduce the risk of vaccination adverse reactions, and is suitable for the prevention of herpes zoster in the elderly and immunodeficient populations.

The present invention provides various compositions and methods useful for the treatment of pancreatic cancer, such as pancreatic ductal adenocarcinoma (PDAC), and methods for activating pancreatic tissue-specific anti-tumor T cell immunity. In some embodiments such methods involve administration of IL33. In some embodiments such methods involve administration of a PD-1 and / or PD-L1 inhibitor.

The invention relates to an mRNA (messenger ribonucleic acid) vaccine containing a proteasome targeting structural domain as well as a preparation method and application thereof. The invention provides a nucleic acid molecule comprising a coding sequence of at least one antigen peptide and a coding sequence of at least one proteasome targeting domain. The mRNA vaccine can increase the presentation rate of antigen peptide, enhance T cell immunity, and improve the killing effect on tumor cells and the immunocompetence on exogenous viruses.

The invention relates to the technical field of vaccines, and particularly discloses a preparation method and application of a tumor cell vaccine, the preparation method comprises the steps of collecting breast cancer cells in a growth index phase, preparing a cell suspension, performing radiation treatment, uniformly mixing the cells and the like, and single-time high-dose (40Gy) radiation is adopted as an inactivation mode; the completeness of a cell structure and the diversity of antigens can be kept to the greatest extent while the proliferation capacity of tumor cells is thoroughly destroyed. The prepared vaccine can strongly activate organism specific T cell immunity and significantly increase the number of IFN gamma < + > CD8 < + > T cells in peripheral blood and tumor local microenvironments, so that an immunosuppressive'cold tumor 'microenvironment is reversed to an immunoactivated'hot tumor' microenvironment, and resistance of breast cancer brain metastasis to immunotherapy is overcome.