82 results about "Major histocompatibility" patented technology

The invention belongs to the technical field of biological medicines, and particularly relates to an anti-fibrosis peptide fragment, a vaccine and a preparation method and application of the peptide fragment vaccine. In order to explore that the peptide fragment is used as a peptide fragment vaccine for fibrotic diseases, the invention provides an anti-fibrosis peptide fragment, a vaccine and a preparation method and application of the peptide fragment vaccine. According to the application disclosed by the invention, main histocompatibility compound restrictive peptide fragments from six protein sources of fibrosis-specific MAF, FNDC3A, TOP2A, TNS3, APBB2 and OLFML2b are taken as targets for treating and preventing fibrosis diseases, and the six peptide fragments are taken as vaccines, so that various fibrosis diseases are remarkably prevented and treated by inhibiting pathological change and collagenous fiber deposition caused by fibrosis, and the application has the advantages that the application range is wide, and the application prospect is wide. Fibrosis of lung, liver, pancreas and the like is included. The peptide fragment and the peptide fragment vaccine provided by the invention provide candidate schemes for future research on preventive and therapeutic vaccine transformation of fibrotic diseases.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors as well as genetically edited or otherwise engineered enhance the persistence the cells in immunotherapy. In several embodiments, the cells are edited to knock out a target gene that encodes a protein involved in antigen processing and presentation by major histocompatibility complex class I molecules. In several embodiments, a mixture of immune cell types is used, optionally in allogeneic therapy. The engineering and editing of the cells, such as NK cells and / or T cells exhibit enhanced cytotoxicity and / or persistence, as well as reduced risk of reduced graft versus host, host versus graft, and graft versus graft effects.

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.

Surrogate co-receptors for T cells, including T cells expressing chimeric receptors comprising major histocompatibility molecules grafted onto T cell receptor molecules. The surrogate co-receptors feature a portion of CD8, wherein the Ig domains of CD8 are replaced with Ig domains that confer novel specificities (e.g. antibody Fv fragments specific for a target of interest.) The surrogate co-receptors may be used to help enhance CRMpMHC-CD3 signaling as part of a 5-module receptor system. The present invention also describes Lck fusions.

This document provides methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as acute myeloid leukemia (AML)). For example, methods and materials for making and / or using T cells expressing (e.g., engineered to express) (a) one or more chimeric antigen receptors (CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more inhibitory CARs (iCARs) having the ability to bind to a class I major histocompatibility complex (MHC) polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, T cells provided herein can be administered to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant to target (e.g., target and destroy) the mammal's myeloid cells while sparing the donor-derived myeloid cells.

The invention provides genetically modified non-human animals that express chimeric human / non-human MHC I polypeptide and / or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

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.

The present invention relates to the therapeutic use of non-classical human major histocompatibility complex (MHC) molecules (also referred to as MHC class Ib molecules) in combination with peptide antigens for the treatment of type 1 diabetes (T1D). The invention more particularly 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 producing such recombinant polypeptides, pharmaceutical compositions comprising same, and their use for treating type 1 diabetes (T1D).

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a humanized T cell co-receptor (e.g., humanized CD4 and / or CD8 (e.g., CD8α and / or CD8β)), a human or humanized T cell receptor (TCR) comprising a variable domain encoded by at least one human TCR variable region gene segment and / or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II α and / or MHC II β chains) and / or MHC I (e.g., MHC Iα) respectively, and optionally human or humanized β2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making a genetically engineered animal that expresses at least one humanized T cell co-receptor (e.g., humanized CD4 and / or CD8), at least one humanized MHC that associates with the humanized T cell co-receptor (e.g., humanized MHC II and / or MHC I, respectively) and / or the humanized TCR are also provided. Methods for using the genetically engineered animals that mount a substantially humanized T cell immune response for developing human therapeutics are also provided.

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.

The application discloses a preparation method and application of a hollow manganese dioxide nanocarrier coated with a human umbilical cord mesenchymal stem cell membrane and a transmembrane peptide TAT, and is characterized in that: hollow mesoporous manganese dioxide is synthesized through a selective etching technology, and a layer of human umbilical cord mesenchymal stem cell membrane is coated outside the manganese dioxide through a repeated extrusion method. Since the cell membrane has special tumor homing characteristics, and lacks major histocompatibility complex-II and only expresses major histocompatibility complex-I in a trace amount, the key scientific problems and difficulties such as low biological safety, strong immunogenicity and easy elimination by the body of artificially synthesized nanomaterials can be effectively solved. Finally, the cell membrane surface is modified with the transmembrane peptide TAT through a phospholipid insertion method, precise subcellular localization-nucleus targeting is realized, and tumor cells can be more effectively killed.

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.

Radionuclide-labeled soluble biologics directed against peptide presenting Major Histocompatibility Complexes (pMHCs), and methods for treating cancers using the biologics are provided. Soluble biologics include recombinant T-cell receptor proteins (rTCR) and TCR-antibody mimics that specifically bind to pMHCs. The soluble biologics may further include a heavy chain of IgG1, IgG2, IgG4, or variants thereof. The radioisotopes used to label the soluble biologic may include alpha-emitting isotopes, such as actinium-225, or beta-emitting isotopes, such as lutetium-177, and may be administered at a maximum tolerated dose in a single bolus or in fractionated doses that together equal the maximum tolerated dose. The methods may further include administration of additional therapeutic agents or modalities.

The present disclosure is directed to antigen-binding molecules that specifically bind peptide fragments of tumor antigens, wherein the peptide fragment is capable of being presented by more than one type of major histocompatibility complex (MHC) class II molecule. In some aspects, the tumor antigen is a WT1 polypeptide. Other aspects are directed to antibodies, multispecific antibodies, and chimeric antigen receptors, and nucleotides encoding the same. Other aspects are directed to methods of administering the same to a subject in need thereof.

Single-domain antibodies that specifically bind human papillomavirus (HPV) E6 or E7 oncogenic peptides in complex with human major histocompatibility complex (MHC) proteins are described. The E6-MHC-specific and E7-MHC-specific single-domain antibodies were isolated from dromedary camel (VHH) antibody libraries by panning the library with an E6- or E7-derived peptide in complex with HLA-A*02:01. Use of the single-domain antibodies for the detection and treatment of HPV-associated cancers and pre-cancerous lesions is also described.

The present invention relates to the therapeutic use of non-classical human major histocompatibility complex (MHC) molecules (also referred to as MHC class Ib molecules) in combination with peptide antigens for the treatment of Parkinson's disease. The present invention more specifically relates to recombinant polypeptides comprising a peptide antigen and one or more domains of a non-classical MHC class Ib molecule. The present invention also relates to methods for producing such recombinant polypeptides, pharmaceutical compositions comprising them, and their use for treating Parkinson's disease.

The present invention provides a T cell receptor (TCR) that binds to immunogenic peptides when presented by major histocompatibility complexes (MHCs).

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.

Major histocompatibility complex-based chimeric receptors (MHC-CAR) for use in targeting autoreactive immune cells. Also provided herewith are genetically engineered immune cells expressing the MHC-CAR for use in treating autoimmune diseases such as multiple sclerosis.

The present disclosure relates to isolated populations of cells comprising stable regulatory T cells and methods of producing the stable regulatory T cells. Some aspects provide an isolated population of cells comprising regulatory T cells (also referred to as Tregs) wherein: the regulatory T cells of the isolated population of cells comprise stable regulatory T cells (a) comprising an exogenous human T cell receptor (TCR) (also referred to as TCR-pMHC) that specifically binds to a target peptide complexed with the major histocompatibility complex (MHC), and (b) comprising a hypomethylated regulatory T cell specific demethylation region (TSDR) at the endogenous FOXP3 locus, at least 80% of the cells of the isolated population of cells being CD25 + / high CD4 + CD127- / lo regulatory T cells, and less than 10% of the cells of the isolated population of cells expressing FOXP3 protein from the engineered FOXP3 locus. The target peptide is typically a specific antigen peptide (agonist) in that it triggers intracellular signaling pathways that induce T cell mediated functions such as cytokine secretion and expression of genes required for inhibitory activity.

The present disclosure relates to a novel vaccine strategy against hepatitis B virus (HBV) infection, which is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. The disclosure provides fusion proteins that target dendritic cells (DCs), the key antigen-presenting cells of the immune system, and deliver HBV-derived peptides to both the major histocompatibility complex (MHC) class I and II pathways, thereby inducing strong and specific humoral and cellular immune responses against the viral envelope and core antigens. The disclosure also provides methods of using the fusion proteins for the prevention or treatment of HBV infection and its complications. The inventors have demonstrated in a mouse model that the DC-targeting HBV vaccine candidates can elicit robust antibody and T cell responses, which are essential for the clearance of the virus and the protection from chronic infection.

The present invention relates to a bispecific polypeptide molecule comprising a first polypeptide chain and a second polypeptide chain providing a binding region derived from a T cell receptor (TCR) being specific for a major histocompatibility complex (MHC)-associated peptide epitope, and a binding region derived from an antibody capable of recruiting human immune effector cells by specifically binding to a surface antigen of said cells, as well as methods of making the bispecific polypeptide molecule, and uses thereof.

The present invention relates to: a composition for delivering a viral antigen-derived CD8+ T cell antigen epitope or a peptide comprising same to the cytoplasm of a target cell to thereby present the epitope or peptide to major histocompatibility complex class I (MAC-1), which is an antigen-presenting molecule on the cell surface; a composition comprising same; and a use thereof.

Methods and systems for peptide binding prediction include predicting (202) a three-dimensional (3D) structure of a peptide and a major histocompatibility (MHC) complex to generate a graph. The 3D structure is refined (204) by pruning edges of the graph having a distance between the peptide and the MHC complex that is below a threshold value. Models for MHC-I and MHC-II binding prediction are trained (206), including Bayesian reweighting of data for the MHC-II binding prediction, using the pruned graph.

An orally bioavailable benzofuran is provided which possesses in vitro and in vivo capabilities able to overcome issues in loading of antigenic peptide on major histocompatibility class I complexes, including on the surface of professional antigen presenting cells. The design of immunotherapies such as dendritic cell vaccines, optimal binding of the antigenic peptides to MHC class I complexes is a major challenge. Current therapeutic peptide loading is expensive, labor-intensive, or requires in vitro manipulation. Models demonstrate that the benzofuran enhances T-cell activation through increased peptide binding to cell surface MHC class I complexes. Molecular docking studies indicate the benzofuran binds the F pocket of MHC class I in a similar manner to high-affinity peptides and TAPBPR, aiding in the targeted loading of exogenous peptides. The therapeutic potential was demonstrated when using PLGA particles of BzFβ were injected intramuscularly, and significantly inhibited the development of E.G7-OVA tumors.

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.

Artificial antigen presenting cells (aAPC) including a major histocompatibility class II (MHC II) molecule and methods of their use for identifying, isolating, or detecting one or more antigen-specific T cells, and treating a disease, disorder, or condition, including cancer, are disclosed.

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.

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.

A bonding prediction device for predicting MHC-peptide complex activity based on artificial intelligence comprises: memory; a communication unit; and at least one processor operably connected to the memory and the communication unit, wherein the at least one processor may be configured to: obtain data related to a structure of a major histocompatibility complex(MHC)-peptide complex, which comprises a first sub-unit and a second sub-unit, from the memory; extract first coordinate information, which is 3D coordinates of the first subunit; extract second coordinate information, which is 3D coordinates of the second subunit; calculate distance information between the first sub-unit and the second sub-unit based on the first coordinate information and the second coordinate information; and perform learning using an artificial intelligence model to predict bonding of the MHC-peptide complex based on the distance information.