71 results about "Histocompatibility" patented technology

The invention relates to the technical field of biomedical materials, and discloses a high-stability porous hydroxyapatite microsphere as well as a preparation method and application thereof, and the porous hydroxyapatite microsphere is formed by self-assembling nano-scale hydroxyapatite particles under the driving of a thermodynamic behavior of reducing excess surface free energy; the porous hydroxyapatite microspheres are nano-scale to micron-scale microspheres with rough surfaces; the porous hydroxyapatite microspheres have a nano-scale pore channel structure; the mineralization is improved under the assistance of the porous hydroxyapatite microspheres; the defects that hydroxyapatite microspheres in the prior art are sharp in microstructure, poor in histocompatibility, free of a porous structure and the like are overcome, the preparation method is simple, the safety coefficient of the production process is high, the obtained porous microspheres are stable in structure, various parameters can be adjusted according to requirements, and the method is suitable for industrial large-scale production.

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 belongs to the technical field of biological medicines, and particularly discloses an insulin-like growth factor-1-linker polypeptide-collagen, and the linker polypeptide has an amino acid sequence as shown in SEQ ID No.1. The N end of the designed and synthesized linker polypeptide simulates an IGF-1 receptor structure and can be combined with IGF-1, the C end of the linker polypeptide is rich in lysine residues and can be covalently cross-linked to collagen through glutamine transaminase, the attachment time of the IGF-1 in endometrium is prolonged, and endometrium thickening and endometrium injury repair are effectively promoted. The protein solution for promoting endometrial injury repair provided by the invention can form a stable repair microenvironment on the surface of the endometrial, promote the number recovery of endometrial glands with intrauterine adhesion, reduce the fibrosis ratio and promote the thickening of thin endometrial, has the advantages of high histocompatibility, simplicity in preparation, obvious improvement effect and the like, and can be used for preparing a medicine for treating endometrial injury. The method has no potential toxic influence on cells and has a good clinical application prospect.

The invention relates to the technical field of high polymer materials, in particular to biological glue applied to fixation of an esophageal hiatus hernia patch. The biological glue comprises 40 to 60 wt% of fibrinogen, 30 to 50 wt% of a polyethylene glycol polymer, 2 to 8 wt% of an amino-containing small molecule compound, 0.2 to 0.8 wt% of a growth factor and 1 to 3 wt% of glutaraldehyde. The biological glue provided by the embodiment of the invention has excellent mechanical properties and good histocompatibility, and can realize a better patch fixing effect in a hiatus hernia operation, so that postoperative recovery of a patient is guaranteed.

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.

The invention provides a preparation method of a double-layer guided tissue regeneration membrane, the double-layer guided tissue regeneration membrane and application of the double-layer guided tissue regeneration membrane, and relates to the field of biomedical materials. The preparation method comprises the following steps: carrying out enzymolysis treatment on pretreated fish skin by combining an acid method with a restrictive enzymolysis method to obtain telopeptide-removed collagen; carrying out electrostatic spinning on the blended spinning solution of the telopeptide-removed collagen and the polylactic acid to form a loose layer, and carrying out electrostatic spinning on the loose layer by adopting the polylactic acid spinning solution to form a compact layer, so as to obtain a double-layer composite membrane; and crosslinking the double-layer composite membrane to obtain the double-layer guided tissue regeneration membrane. The double-layer guided tissue regeneration membrane has low immunogenicity, good mechanical properties and excellent histocompatibility, the compact layer can play a barrier role and prevent fibroblasts from occupying an osteogenic space, the loose surface can promote cell adhesion and growth and accelerate bone tissue repair, and the interface of the double-layer structure is tightly combined.

The invention discloses a traditional Chinese medicine hydrogel composition for preventing and treating anorectal postoperative wound infection as well as a preparation method and application of the traditional Chinese medicine hydrogel composition. Based on traditional Chinese medicine classical ointment powder and in combination with clinical experience, chemical cutting optimization is performed to form a traditional Chinese medicine compound preparation, and the traditional Chinese medicine compound preparation is wrapped by taking a high polymer material as a skeleton and taking glycerol as a wrapping agent; and a stable temperature-sensitive in-situ hydrogel administration system is formed, so that the combination of the traditional Chinese medicine preparation and the hydrogel is realized, and the problems of the traditional ointment are effectively solved. The traditional Chinese medicine hydrogel composition directly acts on a wound surface, is good in adhesiveness and histocompatibility, and can prolong the residence time of a medicine at a medication part and improve the bioavailability; the active ingredients of the traditional Chinese medicine compound preparation can prevent the formation of bacterial biofilm on the wound surface after anorectal operation and inhibit wound surface infection; the hydrogel dosage form enables the hydrogel to form a moist protective film on a postoperative wound surface and form a microenvironment beneficial to wound surface healing, so that healing is accelerated, rehabilitation is promoted, the pain of a patient is effectively relieved, and the hydrogel has important medical value.

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.

The invention provides a succinate nano-drug as well as a preparation method and application thereof. The succinate nano-drug is prepared from ammonium succinate and sodium oleate through a microemulsion method. When the succinate nano-drug enters tumor cells, pyroptosis can be triggered, and expression up-regulation of a main histocompatibility complex I (MHC-I) can be stimulated. The occurrence of pyroptosis will release a large number of injury-associated molecular patterns (DAMPs) to trigger immune activation; and up-regulation of MHC-I expression can promote immune presentation of tumor cells. Under the combined action of immune activation induced by pyroptosis and MHC-I expression up-regulation, the succinate nano-drug not only can effectively activate whole-body anti-tumor immune response, but also can effectively increase tumor cell antigen presentation, so that tumor growth and metastasis are efficiently inhibited, and the immune checkpoint blocking treatment effect is improved. The succinate nano-drug is simple to prepare, mild in reaction condition, free of heavy metal elements and high in biological safety, and shows a good application prospect.

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.

Provided are agents and methods for preventing or inhibiting a multiple sclerosis (MS)-associated adaptive immune response in a subject in need thereof. In some instances, the agents comprise or consist of a soluble peptide-major histocompatibility complex (pMHC) or multimer(s) thereof. The peptide of the pMHC is one identified as being targeted by MS-associated T-cell receptors (TCRs). The agents may be used alone or may be conjugated or fused to one or more moieties that result in the targeted depletion of T cells expressing the MS-associated TCRs. Other agents such as the MS-associated TCRs or binding domains thereof, and inhibitory immune cells expressing such TCRs are also provided. Aspects of the present disclosure further include methods of treating multiple sclerosis in a subject in need thereof via administration of an agent of the present disclosure.

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.

The present invention relates to a tumor vaccine based on nanovesicles fused with tumor cell and immune cell membranes, and a preparation method and application thereof. The present invention adopts nanovesicles fused with dendritic cells and tumor cell membranes overexpressing CD40L as tumor antigen carriers, has good tissue compatibility and immune organ targeting, CD40L can promote dendritic cells to better exert immune functions; nanovesicles formed based on cell membranes have low research and development costs and simple procedures, and improve clinical conversion application rate; using cell membranes as materials for nanovesicles reduces their cytotoxicity and improves safety; the tumor vaccine based on nanovesicles fused with tumor cell and immune cell membranes of the present invention can also be used to prepare tumor therapeutic drugs.

The present disclosure provides a peptide-major histocompatibility complex (pMHC) polypeptide comprising a KRAS peptide and class I MHC polypeptides. The present disclosure provides fusion molecules comprising a pMHC polypeptide and a heterologous fusion partner. The present disclosure provides single-chain T-cell modulatory polypeptides that comprise a pMHC polypeptide, one or more immunomodulatory polypeptide, and an immunoglobulin (Ig) Fc or a non-Ig scaffold. A TMP is useful for modulating the activity of a T cell, for modulating an immune response in an individual, and / or for treating an individual who has a KRAS-associated cancer.