36 results about "Histocompatibility" patented technology

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 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 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.

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 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.

This invention provides an active polypeptide and its application in the preparation of drugs that promote the repair of endometrial damage, belonging to the field of biomedical technology. The sequence of the polypeptide is as follows: Acetyl-Gly-Phe-Phe-Tyr-Gly-Val-Arg-Lys-Lys-Pro. The active polypeptide of this invention is non-cytotoxic and non-reproductive toxic, and can promote the proliferation of endometrial epithelial cells, restore the number of endometrial glands in cases of intrauterine adhesions, reduce the proportion of fibrosis, and promote the thickening of thin endometrium. Its effects are superior to PDGF protein, and it has advantages such as high tissue compatibility, simple preparation, and significant improvement effects.

This 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 myelin-associated peptide antigens for the treatment of multiple sclerosis (MS), MOG antibody disease, and MOG antibody-positive neuromyelitis optica. More specifically, this invention relates to recombinant polypeptides comprising a peptide antigen and one or more domains of a non-classical MHC class Ib molecule. The invention also relates to methods for preparing such recombinant polypeptides, pharmaceutical compositions comprising such recombinant polypeptides, and their use for the treatment of multiple sclerosis (MS), MOG antibody disease, and MOG antibody-positive neuromyelitis optica.

The invention provides a biomarker for pathological staging judgment of primary biliary cholangitis and application of the biomarker, and belongs to the technical field of biomarkers. The biomarker disclosed by the invention comprises a peroxisome bifunctional enzyme, phosphoenolpyruvate carboxykinase, a receptor expression enhancing protein 6, an HLA (human leukocyte antigen) II histocompatibility antigen gamma chain and a C-X-C motif chemotactic factor 10. According to the method, the improvement of the PBC diagnosis efficiency is taken as a starting point, the serum protein and the N-glycopeptide are taken as screening templates, a more accurate non-invasive PBC pathological staging judgment method is provided, and a theoretical basis is provided for early diagnosis of PBC.

Provided herein are methods and systems for phenotype-agnostic isolation of antigen-specific T cells using the ATTACH assay (Assessment of T cells Tethered to Antigen Class I / II Histocompatibility). Also provided are antigen-specific T cells isolated using the ATTACH assay and methods of their use for treatment of a subject.

Provided is a cell having improved tissue compatibility with a transplantation subject. Specifically, by knocking a polynucleotide encoding a single-chain fusion peptide that mimics HLA-G and / or HLA-E that has an inhibitory effect on the activity (cell damage) of NK cells and macrophages into a region encoding the alpha chain of an HLA class I molecule, it is possible to inhibit the expression of the alpha chain of the HLA class I molecule while expressing the single-chain fusion peptide.

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, in particular of hematological neoplasms, such as acute myeloid leukemia (AML). The present invention furthermore relates to tumor-associated T-cell peptide epitopes 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 invention discloses a pMHC binding agent and application thereof. The antigen peptide-major histocompatibility complex binding agent comprises four RNA molecules, wherein the first RNA molecule comprises an antigen peptide, a DRB1 * 13: 02 beta chain, a mouse I-Eb binding segment and nucleic acid molecules coded by CD28 and CD3 zeta proteins of transmembrane and intracellular segments; the second RNA molecule comprises CMV, CD74, an antigen peptide and a nucleic acid molecule coded by a red visible spectrum fluorescent protein; the third RNA molecule comprises CD4 and a nucleic acid molecule coded by a T cell surface receptor binding region peptide sequence; and the fourth RNA molecule comprises mCD40L and a nucleic acid molecule coded by a binding peptide fragment for recognizing pMHC. According to the present invention, the antigen peptide-major histocompatibility complex II type molecule and the T cell surface receptor can be efficiently and specifically combined so as to promote the activation of the target cell surface receptor so as to achieve the efficient autoimmune reaction;

The invention belongs to the technical field of biological medicine, and particularly relates to a polypeptide degradation agent for targeted degradation of CD26 as well as a preparation method and application thereof, and the polypeptide degradation agent is obtained by coupling tetrapeptide and lenalidomide; the amino acid sequence of the tetrapeptide is any one of SEQ ID NO. 1 and SEQ ID NO. 2. The polypeptide degradation agent disclosed by the invention can be used for specifically degrading DPP4, namely CD26 in a targeted manner; however, isoenzymes DPP7, DPP8, DPP9 and the like of DPP4 cannot be degraded, and high selectivity of the isoenzymes DPP7, DPP8, DPP9 and the like is embodied. Besides, the polypeptide degradation agent is small in molecular weight, one end of the polypeptide degradation agent is a natural short peptide, the polypeptide degradation agent has good histocompatibility, target protein can be rapidly degraded within 6 hours, and good tissue permeability is embodied.

The invention provides a therapeutic cell as well as a preparation method and application thereof, a T cell and an NK cell can be combined for use by constructing a chimeric antigen recipient cell for secreting a bispecific immune cell adapter, and T / NK cell combined redirection is realized to treat tumors. Compared with various single immune cell redirection therapies, the method has the advantages that the dependence on the number of autologous T cells is reduced while the excellent anti-tumor efficacy is achieved, the defects that the lifetime of NK cells is short and the half-life period of a bispecific antibody is short are overcome, the histocompatibility and safety are improved, and the application prospect is wide. In addition, the immune escape problem caused by tumor antigen deletion and mutation can be better solved, and clinical requirements are met.