51 results about "Histocompatibility" patented technology

The invention provides a methacrylic anhydride modified sclera extracellular matrix repair material and a curing method thereof, and belongs to the technical field of medical repair materials. The methacrylic anhydride modified sclera extracellular matrix repair material provided by the invention is prepared from the following raw materials: a methacrylic anhydride modified sclera extracellular matrix, methacrylated gelatin, a photoinitiator and a solvent. The sclera extracellular matrix modified by methacrylic anhydride is adopted, methacrylic anhydride contains methacrylic acid, double bonds can be introduced, the sclera extracellular matrix has the photo-initiation polymerization capacity, and in-situ gelling can be carried out at sclera and cornea damage positions under the action of a photoinitiator; the sclera extracellular matrix has good biocompatibility and histocompatibility, so that sclera matrix cells and corneal epithelial cells are adhered and proliferated, and the sutureless repair is realized; the methacrylated gelatin can provide a photo-crosslinking gelatin network under the action of a photoinitiator, so that cell adhesion and proliferation can be promoted, and repair is realized.

The invention relates to the technical field of biomedicine, in particular to a cross-linked modified artificial valve and a preparation method and application thereof. The preparation method comprises the following steps: firstly, preparing a novel compound POSS-PEG-NHS, and carrying out esterification reaction on a-NHS group of the compound and a-NH2 group on the surface of the decellularized porcine valve to realize covalent binding; then, an inherent reducing agent glutathione in an organism is added, and the cross-linked modified artificial valve PPN-GSH-AV is obtained. The valve shows excellent cell safety and blood compatibility, and has obvious advantages compared with a traditional glutaraldehyde cross-linked valve. In-vivo experiments show that the PPN-GSH-AV has high biological safety and histocompatibility, and can effectively reduce immunological rejection. In addition, the valve can relieve oxidative stress of macrophages and promote M2 type transformation, so that inflammatory response is relieved. In clinical application, the PPN-GSH-AV shows a good anti-inflammatory effect and excellent anti-calcification performance, in-vitro pulsating flow test results meet international standards, and the PPN-GSH-AV has clinical transformation potential and wide application prospects.

Described herein are methods for treating an autoimmune or inflammatory disease in a patient, comprising administering a composition comprising: a) a plurality of antigen-major histocompatibility class II complexes (antigen-MHCIIs), each antigen-MHCII of the plurality comprising a ubiquitous autoantigen associated with a binding groove of an MHC class II molecule, wherein the ubiquitous autoantigen is chosen from PDC-E2353-367, PDC-E272-86, and PDC-E2422-436 for DRB3*0202; PDC-E2353-367, PDC-E280-94, and PDC-E2535-549 for DRB5*0101; PDC-E2629-648, PDC-E2122-135, and PDC-E2249-263 for DRB4*0101; and PDC-E2249-263 for DRB1*0801; and b) a nanoparticle core possessing a diameter of between 1 and about 100 nanometers; wherein the antigen-MHCs are coupled to the nanoparticle core or a biocompatible layer surrounding the nanoparticle core; and wherein the autoimmune or inflammatory disease is chosen from multiple sclerosis and psoriasis.

Therapeutic polypeptides, compositions thereof and methods of use thereof for activating NK cells and treating tumors are provided. The therapeutic polypeptides can include a first domain for binding NKG2D and a second domain for binding a tumor target.

The present invention relates to the therapeutic use of non-classical human major histocompatibility complex (MHC) molecules (also known as MHC class Ib molecules) in combination with a peptide antigen for the treatment of neuromyelitis optica (NMO). More specifically, the present invention relates to recombinant polypeptides comprising a peptide antigen in combination with one or more domains of a non-classical MHC class Ib molecule. The present invention also relates to methods of producing such recombinant polypeptides, pharmaceutical compositions comprising such recombinant polypeptides, and their use in the treatment of neuromyelitis optica (NMO).

The present invention relates to therapeutical uses of non-classical human major histocompatibility complex (MHC) molecules (also named MHC class Ib molecules) in combination with myelin-associated peptide antigens for the treatment of multiple sclerosis (MS), MOG antibody disease and MOG antibody positive neuromyelitis optica. The invention more specifically relates to recombinant polypeptides comprising peptide antigens and one or more domains of a non-classical MHC class Ib molecule. The invention also relates to methods of producing such recombinant polypeptides, pharmaceutical compositions comprising the same, as well as their uses for treating multiple sclerosis (MS), MOG antibody disease and MOG antibody positive neuromyelitis optica.

The invention discloses a construction method of mitochondrial nano vesicles Pep-1 (at) TMZm (at) MitoNVs capable of enhancing penetration of blood brain barriers, belongs to the field of preparation of nano drug delivery systems of targeted glioblastoma, and relates to a construction method of nano particles modified and linked with modified temozolomide and Pep-1. According to the mitochondrial nano-vesicle of the Pep-1 (at) TMZm (at) MitoNVs, provided by the invention, the mitochondrial nano-vesicle which can carry temozolomide and has relatively high bioavailability, relatively good histocompatibility, considerable drug loading ratio and encapsulation efficiency and relatively light toxic and side effects is developed; the mitochondrial nano-vesicle based on TMZ modification and Pep-1 is an effective carrier capable of improving the blood brain barrier penetrating capability of a clinical first-line chemotherapeutic drug TMZ and the tumor targeting property and enhancing the anti-tumor activity of the clinical first-line chemotherapeutic drug TMZ.

The invention discloses a modified gelatin liquid metal biomedical nerve adhesive and a preparation method thereof, belongs to the technical field of biomedical materials, and aims at solving the technical problems that an existing nerve tissue adhesive is low in adhesion strength, lack of conductivity and the like. According to the method, gelatin is used as a biocompatible matrix, and the reaction activity of the gelatin is improved through amination modification; lipoic acid is used as a main cross-linking component, a controllable polymer network structure is constructed by using the thermal initiation ring-opening polymerization characteristic of the lipoic acid, and tannic acid is used as a cross-linking agent to assist in regulating and controlling the pre-reaction degree; meanwhile, by adopting a mode of coating the liquid metal nanoparticles with tannic acid, the material is endowed with good conductivity, and the combination of the liquid metal and the organic matrix is enhanced at the same time. By accurately controlling the pre-reaction and deep polymerization process, the obtained adhesive has good histocompatibility and neural signal transduction capability, and has potential application value in the fields of nervous tissue repair and regeneration.

The invention provides a cascade response self-assembly polypeptide for remodeling tumor cell antigen composition, a bioactive solution of the cascade response self-assembly polypeptide and application of the cascade response self-assembly polypeptide. The polypeptide sequentially comprises a hydrophobic end-capping group, an alkaline phosphatase response self-assembly polypeptide sequence, a reduced glutathione response sequence and a T cell epitope peptide sequence. The polypeptide can respond to high-expression alkaline phosphatase in a tumor microenvironment to generate self-assembly and promote efficient internalization of cells; then, the antigen peptide is released under the action of reductive glutathione in tumor cells, and the antigen complex is given to the tumor cells through a main histocompatibility complex I-type molecular antigen presentation pathway. In addition, the specific hydrophobic end-capping group can up-regulate expression of I-type molecules of main histocompatibility complexes of tumor cells, enhance antigen presentation and remarkably enhance the recognition and killing efficiency of antigen-specific T cells on the tumor cells. Combined adoptive immunity and immune checkpoint inhibitor therapy is suitable for combined immunotherapy of solid tumors.

The invention discloses an anti-psoriasis tolerant dendritic cell as well as a preparation method and application thereof, and belongs to the technical field of biological medicines. The tolerant dendritic cell is obtained by in-vitro induction of an immunomodulator and is loaded with a psoriasis-related antigen; wherein the psoriasis related antigen is antibacterial peptide LL37, own nucleotide or a compound of the antibacterial peptide LL37 and the own nucleotide. The tolerable dendritic cell can inhibit type II expression of costimulatory molecules and main histocompatibility complexes and induce generation of regulatory T cells, so that the effects of treating psoriasis and effectively inhibiting relapse of psoriasis are achieved. Therefore, the tolerant dendritic cell provided by the invention has a good application prospect, and provides a brand new direction for treatment of psoriasis.

The present invention belongs to the technical field of biomedical functional dyes and probes, and relates to a fluorescent probe, specifically a cyclodextrin-based near-infrared fluorescent probe. The near-infrared fluorescent probe is a conjugate in which a fluorescent molecule is encapsulated by cyclodextrin. In the near-infrared fluorescent probe of the present invention, the cyclodextrin is embedded onto a carbon chain of the fluorescent molecule, which improves the water solubility, histocompatibility and safety, enhances the fluorescence lifetime and photostability, and achieves rapid delivery and response in ureters, lymphatic vessels and lymph nodes in vivo. The near-infrared fluorescent probe can be used for NIR-I and NIR-II imaging. In addition, the near-infrared fluorescent probe can be labeled with various tumor-targeting molecules to form targeted near-infrared fluorescent probes, thereby achieving precise targeted fluorescence imaging in both NIR-I and NIR-II windows for different types of tumors such as genitourinary tumors, head and neck cancer, breast cancer and cervical cancer, and metastatic lymph nodes. The near-infrared fluorescent probe can be used for the navigation of fluorescence imaging during clinical surgeries.

The invention belongs to the field of biological medicine, and relates to treatment of skin flap avascular necrosis. The invention discloses a preparation method of an autologous dermal nitroglycerin sustained-release microneedle patch and application of the autologous dermal nitroglycerin sustained-release microneedle patch in prevention and treatment of skin flap avascular necrosis. The autologous dermal nitroglycerin sustained-release microneedle patch comprises a polyacrylic acid polymer base and a conical microneedle arranged on one side of the base, the conical microneedle is prepared from a mixture containing nitroglycerin, sodium hyaluronate and autologous nano dermis through a freeze-drying process. According to the autologous dermal nitroglycerin sustained-release microneedle, the histocompatibility of the microneedle is improved through application of autologous dermis, targeted and sustained release of nitroglycerin in a skin flap area is achieved through the microneedle, and skin flap avascular necrosis can be effectively prevented and treated; the method has remarkable advantages and good application prospects in the aspects of improving local drug concentration, improving the survival rate of skin flaps, reducing side effects and simplifying the treatment process.

The present invention relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present invention relates to the immunotherapy of cancer. The present invention furthermore relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

Provided in the present invention is a near-infrared fluorescent probe, relating to the technical field of biomedical functional dyes. In the fluorescent probe, multi-arm polymers having different molecular masses are conjugated to near-infrared or infrared fluorescent molecules; thus, the probe has better water solubility, better histocompatibility, improved safety, a longer fluorescence lifetime, and higher photostability while also achieving rapid delivery and response in the ureter, lymph vessels, and lymph nodes in the body, and can be used for imaging in NIR-I (850-1000 nm) and NIR-II (1000-1700 nm). The fluorescent probe can further label various tumor-targeting molecules to obtain a targeting near-infrared fluorescent probe, thereby achieving precise targeted fluorescence imaging of different types of tumors such as genitourinary tumors, head and neck cancers, breast cancer, cervical cancer, and ovarian cancer, and of metastatic lymph nodes in the NIR-I and NIR-II windows, and can be used in clinical intraoperative fluorescence imaging navigation.

To provide cells having reduced immunogenicity and methods for producing such cells, compositions, and methods for treating kidney disease, to provide regenerative effects to a native kidney for the treatment of chronic kidney disease.SOLUTION: Provided herein are: bioactive renal cells (BRCs) in which a gene encoding a protein within a major histocompatibility complex (MHC) class I molecule or a MHC class II molecule is modified; and methods for producing the same. The genetically modified BRC comprises a heterologous polynucleotide (for example, a plasmid or a viral vector) that expresses an RNA interference (RNAi) molecule that reduces expression of the gene in the BRC.SELECTED DRAWING: Figure 10

The present invention relates to engineering synthetic MHC molecules with novel peptide binding properties, by exploring combinations of groove specificities from naturally occurring MHC-I alleles using structure-guided modeling and design. The invention also relates to generating a chimera, each involving computer implementation, storage of data on a memory device, and the data including data set(s) for making comparisons and accepting or rejecting structures, and with each involving synthesis and expression, including as herein further discussed:

The present disclosure relates to the identification of single nucleotide polymorphisms (SNPs) in the Gamma genomic block in the central region of the major histocompatibility complex (MHC) that can be used for matching transplant donors and recipients and determining disease susceptibility.

Systems and methods for t-cell receptor complex optimization using quantum variational autoencoders. Mixed-state t-cell receptor (TCR) embeddings and mixedstate major histocompatibility complex peptide (pMHC) embeddings can be generated (110) by embedding input TCR sequences and input pMHC sequences, respectively, using a quantum variational autoencoder (QVAE). A combinatorial optimization of the mixed-state TCR embeddings while fixing the mixed-state pMHC embeddings can be performed (120) using a machine learning-based predictor. TCR sequences from the mixed-state TCR embeddings and the mixed-state pMHC embeddings, after the combinatorial optimization, can be decoded (130) using the QVAE to generate an optimized TCR sequence. The optimized TCR sequence can be synthesized (140) as a synthetic compound for downstream tasks.

The present disclosure relates to immunology, particularly to methods for predicting whether a therapeutic protein is likely to elicit an immunogenic response. An exemplary method for predicting amino acid-immune protein complex (IPC) interactions may include accessing a set of amino acid sequences, accessing immune protein complex (IPC) sequences identified for a subject IPC, processing the set of amino acid sequence representations to generate a set of transformed amino acid sequence representations based on a set of element concentration scores representing binding cores of the set of amino acid sequence representations, processing the IPC sequence representations to generate the transformed IPC sequence representations, generating a composite representation, and determining one or more predicted amino acid-IPC interactions based on the composite representations.

A neoantigen model discrimination method to determine if the immune system can discriminate it from “self” by estimating if a neoantigen has sufficient antigenic distance from its wild-type peptide to differentially bind the MHC or activate a T cell. In one embodiment, a model can be integrated to estimate the fitness of tumor clones as the aggregate of the cost due to T cells recognizing high quality neoantigens offset by the gain from mutations in canonical oncogenes. In an additional embodiment, a model can be used to rationally identify antigens that either elicit desired, or prevent undesired responses of any immunologically based medicine.

Novel nucleic acid compositions, vector systems, modified cells, isolated peptides, isolated nucleic acid sequences and pharmaceutical compositions that encode or express T cell receptor components directed against haematopoietic-restricted minor histocompatibility antigens (MiHAs) are provided herein. These novel components may be used in the treatment of a subject having a haematological malignancy, particularly after the subject has undergone allogeneic stem cell transplantation (alloSCT). Associated methods for treating such subjects are also provided herein.

A near-infrared fluorescent probe, relating to the technical field of biomedical functional dyes. In the fluorescent probe, multi-arm polymers having different molecular masses are conjugated to near-infrared or infrared fluorescent molecules; thus, the probe has better water solubility, better histocompatibility, improved safety, a longer fluorescence lifetime, and higher photostability while also achieving rapid delivery and response in the ureter, lymph vessels, and lymph nodes in the body, and can be used for imaging in NIR-I (850-1000 nm) and NIR-II (1000-1700 nm). The fluorescent probe can further label various tumor-targeting molecules to obtain a targeting near-infrared fluorescent probe, thereby achieving precise targeted fluorescence imaging of different types of tumors and of metastatic lymph nodes in the NIR-I and NIR-II windows, and can be used in clinical intraoperative fluorescence imaging navigation.

The present description relates to peptides, proteins, nucleic acids and cells for use in immunotherapeutic methods. In particular, the present description relates to the immunotherapy of cancer. The present description further relates to tumor-associated T-cell peptide epitopes, alone or in combination with other tumor-associated peptides that can for example serve as active pharmaceutical ingredients of vaccine compositions that stimulate anti-tumor immune responses, or to stimulate T-cells ex vivo and transfer into patients. Peptides bound to molecules of the major histocompatibility complex (MHC), or peptides as such, can also be targets of antibodies, soluble T-cell receptors, and other binding molecules.

The present invention relates to the field of biomedical technology, and in particular to a cross-linked modified artificial valve, a preparation method and an application thereof. The present invention first prepares a new compound POSS-PEG-NHS, which undergoes an esterification reaction with the NH2 group on the surface of a decellularized porcine valve through its ‑NHS group to achieve covalent bonding. Subsequently, glutathione, a reducing agent inherent in the organism, is added to obtain a cross-linked modified artificial valve PPN-GSH-AV. The valve exhibits excellent cell safety and blood compatibility, and has obvious advantages over traditional glutaraldehyde cross-linked valves. In vivo experiments have shown that PPN-GSH-AV has high biosafety and tissue compatibility, and can effectively reduce immune rejection reactions. In addition, the valve can also reduce the oxidative stress of macrophages, promote M2 transformation, and thus reduce inflammatory reactions. In clinical applications, PPN-GSH-AV exhibits good anti-inflammatory effects and excellent anti-calcification properties, and the in vitro pulsatile flow test results meet international standards. It has the potential for clinical transformation and has broad application prospects.

The present invention relates to granulocyte precursor cell that has been differentiated in vitro, wherein the granulocyte precursor cell comprises: (a) increased expression of one or more of: serglycin (SRGN), myeloperoxidase (MPO), major histocompatibility complex, class II, DR alpha (HLA-DRA), CD74, and elastase (ELANE) when compared to an equivalent granulocyte precursor cell that has been differentiated in vivo; and / or (b) decreased expression of one or more of: defensin alpha 1 (DEFA1), defensin alpha 3 (DEFA3), cathelicidin antimicrobial peptide (CAMP), bactericidal permeability increasing protein (BPI), and azurocidin 1 (AZU1) when compared to an equivalent granulocyte precursor cell that has been differentiated in vivo. Also provided are cells, methods for producing the same, uses of the same, and kits comprising the same.

The invention discloses a transcription template DNA (Deoxyribose Nucleic Acid) of an LMP1 (Lipoprotein Protein 1) antigen mRNA (Messenger Ribonucleic Acid) and the LMP1 antigen mRNA obtained by transcription of the transcription template DNA. The transcription template DNA is formed by sequentially connecting a promoter, a 5'end non-coding region, a human tissue plasminogen activator gene secretion signal peptide, an LMP1 antigen coding region, a main histocompatibility complex I-type transport signal, a 3 'end non-coding region, a poly (adenylic acid) tail and a terminal sequence; the human tissue plasminogen activator gene secretion signal peptide, the LMP1 antigen coding region and the main histocompatibility complex type I transport signal are connected through a GS flexible linker. The LMP1 antigen mRNA disclosed by the invention efficiently expresses the LMP1 antigen and induces specific immune response in a body. The invention also discloses an application of the LMP1 antigen mRNA in preparation of drugs for preventing and / or treating EBV-related tumors.

The present invention relates to engineering synthetic major histocompatibility complex (MHC) molecules for generating universal peptide / MHC complexes with engineered disulfide linkage(s) using structure-guided modeling and design and method for making and using the same.

Systems and methods for t-cell receptor complex optimization using quantum variational autoencoders. Mixed-state t-cell receptor (TCR) embeddings and mixedstate major histocompatibility complex peptide (pMHC) embeddings can be generated (110) by embedding input TCR sequences and input pMHC sequences, respectively, using a quantum variational autoencoder (QVAE). A combinatorial optimization of the mixed-state TCR embeddings while fixing the mixed-state pMHC embeddings can be performed (120) using a machine learning-based predictor. TCR sequences from the mixed-state TCR embeddings and the mixed-state pMHC embeddings, after the combinatorial optimization, can be decoded (130) using the QVAE to generate an optimized TCR sequence. The optimized TCR sequence can be synthesized (140) as a synthetic compound for downstream tasks.

The invention provides a near-infrared fluorescent probe, and relates to the technical field of biomedical functional dyes. According to the fluorescent probe, multi-arm polymers with different molecular weights are coupled with near-infrared or infrared fluorescent molecules, so that the fluorescent probe has better water solubility, higher histocompatibility and safety, longer fluorescence lifetime and higher light stability, and meanwhile, rapid transmission and response in ureters, lymphatic vessels and lymph nodes in vivo are realized; the method is used for imaging of NIR-I (850 nm to 1000 nm) and NIR-II (1000 nm to 1700 nm). The fluorescent probe is further marked with various tumor targeting molecules to obtain a targeted near-infrared fluorescent probe, so that accurate targeting fluorescence imaging of different types of tumors such as urogenital tumors, head and neck cancers, breast cancers, cervical cancers and ovarian cancers and metastatic lymph nodes in NIR-I and NIR-II windows can be realized; the method is applied to clinical intraoperative fluorescence imaging navigation.