246 results about "Antigen-presenting cell" 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 relates to the technical field of biology, in particular to a tumor postoperative vaccine as well as a preparation method and application thereof. The method comprises the following steps: resuspending tumor cells in a first solution containing metal ions for incubation, collecting the tumor cells, resuspending the tumor cells in a second solution containing mineralized ions for incubation, enabling the metal ions to react with the mineralized ions to obtain metal inorganic salt, forming a mineralized shell layer on the surfaces of the tumor cells, and resuspending the tumor cells to obtain the tumor postoperative vaccine. And due to the mineralized shell layer, the vaccine has the capability of activating a signal channel in an antigen presenting cell through mechanical stimulation, so that an immune system is favorably activated, and the anti-tumor capability of the vaccine is improved. In addition, tumor cells are inactivated in the vaccine preparation process and keep a complete form, and presentation of a complete tumor antigen is facilitated, so that a relatively good anti-tumor effect is obtained.

The invention provides a porcine deltacoronavirus S1 protein nanoparticle vaccine CTDnps and application thereof, and belongs to the technical field of vaccine preparation. The PDCoV S1 protein C-terminal structural domain nanoparticle vaccine capable of being self-assembled, provided by the invention, comprises ferritin and a PDCoV S1 protein C-terminal structural domain, the amino acid sequence of the ferritin is as shown in SEQ ID NO.1, and the amino acid sequence of the PDCoV S1 protein C-terminal structural domain is as shown in SEQ ID NO.2. The PDCoV S1 protein C-terminal structural domain nanoparticle vaccine capable of being self-assembled comprises the ferritin and the PDCoV S1 protein C-terminal structural domain. The PDCoV S1 protein C-terminal structural domain nanoparticle vaccine (S1CTD-Fer) constructed by the invention can be self-assembled to form ferritin-like cage-shaped nanoparticles, and the hydrodynamic diameter of the cage-shaped nanoparticles is obviously greater than that of natural ferritin nanoparticles. Compared with the S1CTD, the S1CTD-Fel based on the ferritin carrier can obviously enhance the immunogenicity of the S1CTD, can obviously enhance the uptake efficiency of antigen presenting cells, and is high in safety.

The invention discloses an emulsifier for preparing a Pickering emulsion, the Pickering emulsion as well as a preparation method and application of the Pickering emulsion. The emulsifier of the Pickering emulsion is obtained by dissolving distearoyl phosphatidylcholine, cholesterol and distearoyl phosphatidyl ethanolamine-polyethylene glycol 2000 in ethanol, carrying out rotary evaporation to remove ethanol, then adding an antigen aqueous solution containing an antigen, continuing rotary evaporation to obtain liposome nanoparticles, heating the liposome nanoparticles with mannose in a water bath, and carrying out freeze drying. The Pickering emulsion is obtained by dispersing an emulsifier in water as a water phase, taking squalene as an oil phase, mixing the water phase and the oil phase, and homogenizing. The Pickering emulsion disclosed by the invention is prepared by taking antigen presenting cell targeted liposome nanoparticles as a raw material; and the antigen has excellent ion concentration characteristic, pH stability, temperature stability and storage stability, and can protect the integrity of the antigen.

The invention relates to the technical field of biological medicine, and provides a Chinese herbal medicine vesicle-LNP hybrid tumor mRNA vaccine and application thereof. The tumor mRNA vaccine disclosed by the invention is obtained by hybridizing Chinese herbal medicine nano-vesicles and lipid nano-particles loaded with tumor antigen mRNA. According to the invention, the characteristic of good biocompatibility of Chinese herbal medicines is utilized, so that the safety risk of the cationic lipid carrier is reduced. By combining the characteristics of Chinese herbal medicines, the nano-vesicles are extracted, so that the LNP is promoted to more effectively target antigen-presenting cells, the uptake level of the antigen-presenting cells is promoted, the phagocytosis of mRNA is enhanced, and the targeting and transcriptional expression level of mRNA can be enhanced. Finally, the Chinese herbal medicine nano vesicle-LNP hybrid tumor mRNA vaccine can strengthen the curative effects of inhibiting tumor progression, tumor recurrence and tumor metastasis after the tumor mRNA vaccine is inoculated, and a path is opened up for the combination of the tumor mRNA vaccine and richer immunotherapy means.

Disclosed are a metal-polyphenol nano-coating-wrapped tumor whole cell, a preparation method therefor, and use thereof. A plant polyphenol in the present invention and manganese ions can be rapidly assembled at room temperature to form a dense coating on the membrane of a tumor cell. The nano-coating wrapping inactivates the tumor cell, ensuring that the vaccine is safe. The nano-coating can prevent any potential tumor antigen from being lost under physiological conditions. The nano-coating is further modified with a lipopolysaccharide, which can promote the endocytosis of the formed whole-cell vaccine by antigen-presenting cells. While forming the structural coating, ions of the metal manganese can stimulate the STING pathway to enhance the anti-tumor effect.

Two plasmids are transformed in the bacterium, one plasmid is a gene editing plasmid which is used for expressing CRISPR / Cas9 gene editing tools in the bacterium, the sgRNA sequence is shown in SEQ ID NO.1, and the other plasmid is an X174E-CKS9 expression plasmid which is used for expressing targeting peptide shown in SEQ ID NO.2 and IPTG (isopropyl-beta-d-thiogalactoside) induced expression splitting gene X174E in the bacterium. The invention further discloses a cracking vesicle obtained after induction of the engineering bacterium and application of the cracking vesicle. CKS9-loaded lysing vesicles with M cell targeting are generated in situ, and a gene editing tool is transferred to antigen presenting cells by using the characteristic that the M cells can completely transfer antigens to lymphatic follicles. Compared with a strategy of mannose modification and other targeted antigen-presenting cells, the method has the advantages that the targeting property is more accurate, and a new choice is provided for the antigen-presenting cells of targeted intestinal tracts.

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APC's.

The invention belongs to the technical field of cancer immunotherapy, and particularly relates to iterative radiation-resistant tumor cell debris, a preparation method thereof and an application thereof in tumor resistance. The anti-radiation tumor cells generated by repeated radiation exposure show higher TMB (Tetramethylbenzidine) and induce stronger immunoreaction, so that a personalized vaccine is developed based on the method, and the frozen fragment vaccine is obtained by freeze thawing and inactivation of the radiation-resistant tumor cells. The RR-FDV exhibits enhanced immunogenicity as compared to a conventional radiosensitive counterpart. In the present disclosure, RR-FDV exhibits superior activation of antigen presenting cells, while in vivo, it recruits more dendritic cells to the vaccination site, promotes DC-mediated antigen presentation, and induces stronger antigen-specific T cell toxicity.

The invention discloses a nucleic acid vaccine based on different forms of nano-aluminum adjuvants and application thereof, the nucleic acid vaccine is composed of an inner core, a middle layer and a shell from inside to outside in sequence, the inner core is a compound of a cationic polymer and nucleic acid, the middle layer is an anionic polymer, and the shell is a continuous or discontinuous nano-aluminum coating layer. The nano-aluminum-coated nucleic acid delivery system provided by the invention is used for preparing vaccines, can effectively activate antigen presenting cells and promote antigen presentation, so that humoral immunity and cellular immunity processes of an organism are simultaneously activated, the tumor immunotherapy effect is enhanced, and the nano-aluminum-coated nucleic acid delivery system has relatively high clinical use value.

There is an urgent need for an effective therapeutic vaccine against tuberculosis (TB), which remains a major public health problem. Current "classical" strategies under development have failed or are suboptimal, and more effective vaccines are needed to achieve the World Health Organization's 2035 End TB Strategy. We have generated a post-exposure / therapeutic TB vaccine candidate (CD40.TB) whose heavy chain consists of an antibody directed against a surface antigen (i.e., CD40) of antigen-presenting cells (i.e., dendritic cells) conjugated to three relevant Mycobacterium tuberculosis (Mtb) antigens and which is liable to induce potent anti-TB humoral and cellular immunity.

Devices and methods for obtaining immunostimulatory antigen presenting cells. The present invention relates to methods for producing immunostimulatory antigen presenting cells. The invention also relates to the use of such cells for treating a patient suffering from a hyperproliferative disease, such as cancer.

Chronic obstructive pulmonary disease is a major clinical challenge mostly due to cigarette smoke exposure and affects more than 200 million people. The inventors tested if exposure to the Bordetella pertussis BPZE1 strain could modulate outcomes of chronic exposure to cigarette smoke in mice. In particular, they showed in mice chronically exposed to cigarette smoke that preventive and / or curative vaccination using BPZE1 could limit the lung inflammation and strongly contribute to the prevention of lung function decline. BPZE1 vaccination modulated pulmonary antigen presenting cells (macrophages and dendritic cells) to switch the immune response, by decreasing the IL-17 inflammatory pathway involved in the pathology of COPD itself, and by favouring a tolerogenic response (IL-10). Together, the data show that vaccination with BPZE1 of mice chronically exposed to cigarette smoke limits the development of chronic obstructive pulmonary disease outcomes and thus represents an interesting therapy.

Activation of STimulator of INterferon Genes (STING) triggers cytokine production and facilitates tumor antigen cross-presentation. In an embodiment of the present invention, STING-dependent innate immune signaling pathway activators (STAVs) together with Replicants including mRNA adapted to express an antigen can be delivered to antigen presenting cells (APC's) using lipid nanoparticle formulations. In various embodiments of the present invention, the range of cancers amenable to STAV / Replicant therapy can be extended using a non-cell-based nanoparticle strategy that effectively delivers the STAV / Replicant into the Tumor Micro Environment (TME) to potently generate anti-tumor cytotoxic T cell activity together with humoral immune responses. The STAV / Replicant formulations can be introduced into solid tumors present in the subject. Alternatively, the STAV / Replicant can be introduced through direct inoculation, intramuscularly, or intravenously. The lipid nanoparticles stick to the tumor cells and are co-phagocytosed to activate STING in APCs.

The application provides a hyaluronic acid artificial lymph node sustained-release nano DNA vaccine for enhancing cancer prevention effect and a preparation method thereof, and the preparation raw materials comprise a plasmid, 4-(bromomethyl)phenyl boronic acid modified linear polyethylene imine, a cell colony stimulating factor, a sulfhydryl modified hyaluronic acid and a four-arm-maleimide grafted polyethylene glycol. The nano DNA vaccine can recruit a large number of immune cells to form a hyaluronic acid artificial lymph node after subcutaneous administration, and inhibit the generation of tumors by continuously outputting antigen presenting cells and antigen specific T cells. In addition, the hyaluronic acid artificial lymph node can also release the nano DNA vaccine, prolong the vaccine stimulation time, improve the problem of weak immunogenicity of the existing DNA vaccine, and also solve the problem of biocompatibility. The nano DNA vaccine has the advantages of easy preparation, easy storage, low price and the like.

The invention relates to a method for the generation of a TCR in a rodent, method comprising delivering an antigen presenting cell (APC) expressing an MHC-peptide complex to the rodent, wherein the MHC component of the MHC peptide is not expressed and generating T-cells to the MHC-peptide complex in the rodent. The method further comprises isolating or purifying the T-cell from the rodent. The MHC component is either allogenic or xenogenic and the MHC expressed in the rodent is a human HLA, such as HLA-A*02:01, HLA-A*11:01, HLA-A*03:01 or HLA-A*24:02. The rodent genome encodes a fully human TCR. The peptide is from a human antigen associated with disease, such as a tumour associated antigen. The rodent genome comprises human CD8 or chimeric CD8. The TCR sequence has been modified by up to 3 amino acids from that identified in the rodent. Also disclosed is a method for generating a TCR in a mouse, identifying the nucleic acid encoding the TCR and then mutating the sequence. The TCR is expressed in the form of a larger molecule. The APC is a synthetic antigen presenting cell.

Provided herein are T cell epitopes associated with Type 1 diabetes. Also provided are antigen-presenting cells presenting such epitopes. T cells reactive to such epitopes, and related compositions and therapies.

A nanoparticle and a preparation method therefor, the nanoparticle including an amphiphilic peptide, which forms a micelle structure through self-assembly, and a target peptide (preferably, a water-soluble antigen peptide), which electrically binds to the surface of the amphiphilic peptide. The target peptide electrically binds to the surface of the amphiphilic peptide micelle structure and becomes particulated, and thus can be effectively presented to an antigen-presenting cell, and the weight ratio of the amphiphilic peptide and the target peptide is controlled so that the size of nanoparticles is controlled and endocytosis thereof is carried out, and thus immunity by means of cytotoxic T cells can be induced. Nanoparticles exhibit use only an epitope of a more accurate region so as to be effective as a vaccine, and thus have minimal side effects. Therefore, excellent antigen-specific antibody and cell immunotherapy effects are exhibited, and thus can be used in various fields such as vaccine production.

The invention relates to a multi-metal element nano-aluminum adjuvant and a preparation method and application thereof, the nano-aluminum adjuvant is a nano-particle containing an aluminum element and at least one metal element selected from magnesium, zinc and calcium, the nano-particle has a layered crystal structure, and the particle size is distributed in a range of 20-2000 nm. The difunctional nano-aluminum adjuvant has the beneficial effects that the difunctional nano-aluminum adjuvant is simple and convenient in preparation method, definite in component and uniform in particle size, the particle size of the particles can be manually regulated and controlled, and the difunctional nano-aluminum adjuvant can directly promote antigen presenting cells to be mature and activated and carry out MHC-I or II type antigen presentation.

Provided herein are compositions and methods for method for inducing intermediate macrophages in a subject, the method comprising: administering to the subject a therapeutically effective amount of one or more compositions that comprise a compound of formula (I) or stereoisomer, enantiomer, tautomer or a pharmaceutically acceptable salt thereof:wherein the compound promotes monocyte differentiation into an antigen-presenting cell (APC)-specific intermediate macrophage lineage.

The invention discloses a hepatocellular carcinoma prognosis and treatment adaptability evaluation model based on mRNA vaccine antigen and a construction method. The method comprises the following steps: firstly, analyzing gene expression difference between normal tissues and hepatocellular carcinoma tumors, understanding mutation and genome structure change of hepatocellular carcinoma patients, and then further selecting genes related to the infiltration level of antigen presenting cells from abnormally expressed genes and mutant genes, and the genes having a significant relationship with the overall lifetime and disease-free lifetime of the patient, so as to obtain candidate mRNA vaccine neoantigen targets. Based on the expression level of the target, immunotyping is performed on the patient, and the patient population suitable for the mRNA vaccine is evaluated. Meanwhile, the relationship between the expression level of the target spot and the prognosis of the patient is quantified, so that the probability value that the total survival time of the hepatocellular carcinoma patient reaches 3 years and 5 years is predicted. According to the invention, the hepatocellular carcinoma treatment resistance and tumor immune state can be objectively and accurately evaluated, and the prediction accuracy of hepatocellular carcinoma treatment prognosis is improved.

The invention discloses a novel benzothiazole compound as well as a preparation method and application thereof. According to the novel benzothiazole compound, through targeted activation of an RIG-I / OAS innate immune pathway, expression of key proteins and genes such as OAS1 and RIG-I can be rapidly up-regulated, secretion of type I interferon and proinflammatory factors is induced, and instant immune enhancement is achieved; more importantly, by performing long-term functional reprogramming on innate immune cells (such as mononuclear cells and dendritic cells), persistent'innate immune memory '(namely immune domestication) can be induced. The dual-action mechanism can significantly enhance the activation of antigen presenting cells and promote the generation and long-term maintenance of memory B cells and effector memory T cells, has no significant toxicity to liver functions, can be used as an immunologic adjuvant and an immunodomestication molecule of an RSV vaccine, can synergistically improve the vaccine-induced RSV specific antibody titer and neutralizing antibody level, and can be used for preparing an immunologic adjuvant for the RSV vaccine. Long-acting immune protection is provided, and a brand new solution is provided for research and development of RSV vaccines.

The invention relates to the field of immune cells. According to the preparation method and application of the novel immune cell, lentivirus containing DNA molecules subjected to gene modification is used for transfecting cells in peripheral blood of mammals, so that the cells can be passaged for multiple times, and the cells have the antigen presenting capacity and the capacity of activating and amplifying natural killer cells. After the cell is further genetically modified, better transmembrane transfer, antigen presentation and natural killer cell activation can be realized. After gene modification, the cell and different cytokines or small molecules jointly activate and amplify mononuclear cells to obtain a larger number of natural killer cells with higher purity, epigenetics are regulated and controlled to change the receptor and ligand expression quantity of the natural killer cells, and then the cytotoxicity of effector cells is improved. The invention can be used for preparing antigen presenting cells and CTL cells aiming at different antigens and an application method. The cells and the using method have wide application prospects in the aspects of prevention and treatment of tumors and infectious diseases.

The present invention relates to an immunoglobulin derived single-chain fragment variable (scFv) that broadly binds HLA II molecules and uses thereof. In particular, targeting of an antigen to antigen presenting cells with the HLAII-specific targeting unit provided herein find use in enhancing immune responses after vaccination.

The present invention relates to in vitro methods of producing mature dendritic cells, a dendritic cell maturation cocktail, a method of producing mature antigen presenting dendritic cells in vitro, methods of manufacturing vaccines containing mature dendritic cells, antigen-presenting mature dendritic cells produced according to the methods described, vaccines containing the mature antigen-presenting dendritic cells and methods of treatment and used of mature antigen-presenting cells of the invention.

This invention discloses a prognostic and therapeutic suitability assessment model for hepatocellular carcinoma (HCC) based on mRNA vaccine antigens, and its construction method. First, the differences in gene expression between normal tissues and HCC tumors are analyzed to understand the mutations and genomic structural changes in HCC patients. Then, genes related to the level of antigen-presenting cell infiltration, as well as genes significantly related to overall survival and disease-free survival, are further selected from anomalously expressed and mutated genes to obtain candidate mRNA vaccine neoantigen targets. Based on the expression levels of these targets, patients are immunophenotyped to assess the patient population suitable for mRNA vaccines. Simultaneously, the relationship between target expression levels and patient prognosis is quantified to predict the probability of HCC patients achieving 3-year and 5-year overall survival. This invention can objectively and accurately assess treatment resistance and tumor immune status in HCC, improving the predictive accuracy of HCC treatment prognosis.

The invention discloses a Toll-like receptor (TLR) agonist / organic photosensitizer protein nano-composite as well as a preparation method and application of the Toll-like receptor (TLR) agonist / organic photosensitizer protein nano-composite. In order to overcome the defects of short blood half-life period, low bioavailability and the like of the existing TLR agonist, the protein nano-composite is obtained by forming a compound in a protein cavity by using the TLR agonist and an organic photosensitizer, and has tumor and lymph node dual-targeting characteristics. The protein nano-composite is simple in preparation method, mild in condition, free of an organic solvent, uniform in particle size and has a pH-responsive drug release behavior, and the protein nano-composite is prepared by a one-step method with water as a solvent. Based on an active targeting mechanism mediated by an albumin binding receptor and an active uptake mechanism of antigen presenting cells to albumin, the nano-composite has tumor and lymph node dual-targeting characteristics, has immunotherapy and light therapy effects under irradiation of near-infrared light, and has a good application prospect from two aspects of short-term quick action and long-term body immunity improvement. Tumor growth is effectively restrained, and tumors are expected to be radically treated.

The invention discloses a cell-penetrating peptide CPP137 as well as a compound, a composition and application thereof, and belongs to the technical field of polypeptides. According to the application, a cell-penetrating peptide CPP137 with immune cell selectivity is screened out from a plague bacillus sORF library. The polypeptide not only can be efficiently internalized by THP-1 (M0 type) mononuclear cells, but also can specifically target two key antigen presenting cells, namely primary macrophages and dendritic cells (DC), in a complex human whole blood physiological environment, but is not obviously combined with other blood cell types. Therefore, the cell-penetrating peptide CPP137 is a targeted delivery carrier with great potential, can be used for specifically delivering a therapeutic load to myeloid immune cells, and is used for treating intracellular infection and immune-related diseases or used as a vaccine development platform. Meanwhile, CPP137 can also be used as a specific diagnostic marker or an imaging probe for detecting or tracing pathological states related to macrophages / DC.

The present invention provides a method for expanding anti-tumor T cells comprising the steps of: a) providing a phagocyzable particle having one or more tumor neoantigen constructs in intimate association therewith wherein the tumor neoantigen constructs comprise an amino acid sequence comprising at least one mutant amino acid known or suspected of being associated with cancer in a subject, or a mutated or non-mutated amino acid sequence known or suspected of expression in cancer cells of the subject; b) providing a living antigen presenting cell; c) contacting the particles with the antigen presenting cells in vitro under conditions that allow the antigen presenting cells to phagocytize the particles; d) providing a T cell sample comprising live T cells from the subject; e) contacting the T cell sample with the antigen presenting cells in in vitro contact with the particles under conditions allowing specific activation of the anti-tumor T cells in response to the antigen presented by the antigen presenting cells. The invention also provides tumor neoantigen constructs as defined in the specification.