81 results about "Major histocompatibility complex" patented technology

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a human or humanized T cell receptor (TCR) from a human or humanized TCR locus comprising a non-human TCR non-coding sequence, and optionally a humanized T cell co-receptor (e.g., humanized CD4 and / or CD8 (e.g., CD8α and / or CD8β)), 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 the genetically engineered animals are also provided. Methods for using the genetically engineered animals for developing human therapeutics are also provided.

Provided herein are a fusion polypeptide comprises (i) a first polypeptide comprising LY6K protein; and (ii) a second polypeptide comprising major histocompatibility complex (MHC) class I transmembrane and trafficking domain (MITD), nucleic acids encoding the fusion polypeptide, a vaccine comprising an RNA polynucleotide that encodes the fusion polypeptide, wherein the vaccine is formulated in a lipid nanoparticle, and a method of treating a cancer in the subject by administering to the subject a therapeutically effective amount of the vaccine.

Genetically modified animals and cells with humanized light chain immunoglobulin locus and / or humanized heavy chain immunoglobulin locus. The animals and cells can also express a human or chimeric (e.g., humanized) major histocompatibility complex (MHC) protein complex.

Featured are devices, systems, and methods of use for detecting binding of polynucleotide-peptide conjugate-major histocompatibility complex (pMHC) monomers to a T cell receptors (TCR) on a T cell, and the use of a peptide library to detect binding of antigenic peptides in a pMHC monomer to a T cell receptor (TCR) on a T cell.

The present disclosure relates to immunology, in particular to methods of predicting whether a therapeutic protein is likely to trigger 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 an immune protein complex (IPC) sequence identified against the IPC of the subject; processing a set of amino acid sequence representations to generate a set of converted amino acid sequence representations based on a set of element focusing scores representing binding cores of the set of amino acid sequence representations; processing the IPC sequence representation to generate a converted IPC sequence representation; generating a synthetic representation; and determining one or more predicted amino acid-IPC interactions based on the synthetic representation.

The present invention provides a T-cell receptor (TCR) that binds to an immunogenic peptide when the peptide is presented by the major histocompatibility complex (MHC).

A system for binding peptide search for immunotherapy is presented. The system includes employing a deep neural network to predict a peptide presentation given Major Histocompatibility Complex allele sequences and peptide sequences, training a Variational Autoencoder (VAE) to reconstruct peptides by converting the peptide sequences into continuous embedding vectors, running a Monte Carlo Tree Search to generate a first set of positive peptide vaccine candidates, running a Bayesian Optimization search with the trained VAE and a Backpropagation search with the trained VAE to generate a second set of positive peptide vaccine candidates, using a sampling from a Position Weight Matrix (sPWM) to generate a third set of positive peptide vaccine candidates, screening and merging the first, second, and third sets of positive peptide vaccine candidates, and outputting qualified peptides for immunotherapy from the screened and merged sets of positive peptide vaccine candidates to support downstream clinical decision making.

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).

Herein is reported a method for producing C-terminally biotinylated FcRn comprising the steps of cultivating a mammalian cell comprising a deoxyribonucleic acid encoding FcRn and E. coli biotin-[acetyl-CoA-carboxylase] ligase (BirA) in a biotin containing medium, and recovering C-terminally biotinylated FcRn from the cell or the cultivation medium, wherein the deoxyribonucleic acid encoding FcRn and E. coli BirA is stably integrated into the genome of the mammalian cell and comprises in 5′- to 3′-direction a first expression cassette encoding class I major histocompatibility complex-like protein (α-FcRn) comprising a HisAvi-tag at the C-terminus, a second expression cassette encoding β2-microglobulin (β2m), a third expression cassette encoding class I major histocompatibility complex-like protein (α-FcRn) comprising a HisAvi-tag at the C-terminus, a fourth expression cassette encoding β2-microglobulin (β2m), and a fifth expression cassette encoding E. coli biotin-[acetyl-CoA-carboxylase] ligase.

This disclosure provides a method for treating cancer in human subjects, comprising the administration of a recombinant polypeptide containing a cancer-specific CD8+ T cell epitope. The peptide, recognized by a major histocompatibility complex (MHC) molecule, can activate a T cell immune response to target cancer cells in the subject. This disclosure further provides a cancer-specific CD8+ T cell epitope constrained to an MHC molecule expressed by a specific HLA allele in the subject. This disclosure further provides a composition encoding a recombinant polypeptide capable of inducing an augmented memory CD8+ T cell response.

Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we have developed an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.

The present disclosure provides a peptide-major histocompatibility complex (pMHC) polypeptide comprising a peptide epitope 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, and for modulating an immune response in an individual.

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 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.

This method for predicting T cell activation via peptide-MHC includes the following steps: wherein the analytical device: receives genetic data from a patient; identifies, based on the genetic data, the first amino acid sequence of the major histocompatibility complex (MHC) and the second amino acid sequence of an antigen produced by tumor cells; generates a matrix indicating the interrelationship between the first and second amino acid sequences in units of individual amino acids; and inputs the matrix into a trained neural network model to determine whether T cells secrete at least a threshold amount of cytokines due to the binding of MHC to the antigen.

The present disclosure relates to a genetically modified virus comprising at least one nucleic acid molecule encoding a cytokine that recruits and / or activates T cells and a class II major histocompatibility complex transactivator (CIITA), as well as pharmaceutical compositions comprising said genetically modified virus and methods of treating cancer with said genetically modified virus.

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

Immunogenic response prediction techniques are described. In an example, a system receives first training data that identifies a peptide, a first set of multiple major histocompatibility complex (MHC) molecules, and an immunogenic response associated with the peptide and the first set. The system updates a parameter of a first model based at least in part on the first training data. The first model is configured to determine a probability of causing the immunogenic response by a pair formed by the peptide and a MHC molecule from the first set. The system also receives second data that identifies a second set of MHC molecules, and generates, by using the first model and a second model, an immunologic response prediction of pairing the peptide with a MHC molecule from the second set. The second model is configured to generate at least one of peptide-MHC binding predictions or peptide-MHC cell surface presentation predictions.

Provided herein are T cell receptors (TCRs) or antigen-binding fragments thereof, such as those that recognize or bind NPM1c neoantigens. In particular, the present disclosure relates to TCRs that bind or recognize specific NPM1c peptides in the context of major histocompatibility complex (MHC) molecules. The present disclosure also relates to nucleic acids encoding such TCRs, engineered cells comprising such TCRs, methods of isolating such TCRs, and uses thereof, e.g., in cell therapy.

The invention provides genetically modified non-human animals that express chimeric human / non-human MHC I and MHC II polypeptides 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 an engineered regulatory T cell (Treg) comprising a T cell receptor (TCR) which is capable of specifically binding to a myelin basic protein (MBP) peptide or variant or fragment thereof when the peptide is presented by a major histocompatibility complex (MHC) molecule. The present invention further relates to methods for providing an engineered Treg and to methods and uses of said engineered Treg and vectors and kits of vectors encoding said Treg.

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 relates to the technical field of immunodetection, and discloses a PLA2R antigen epitope peptide for membranous nephropathy and application thereof. The antigen epitope is selected from at least one of Ricin, CTLD1, CTLD7 and CTLD8. The PLA2R antigen epitope of membranous nephropathy can be combined with a self-reaction B cell and is presented to a T helper cell through a major histocompatibility complex (MHC) II type receptor, the stimulated T cell releases cytokines and feeds back the cytokines to the B cell to stimulate division and differentiation of plasma cells and generate an antibody and memory B cells, and a physiological target of immune response of membranous nephropathy is formed. The important value is realized on the diagnosis and prognosis of membranous nephropathy.

RNA encoding an immunogen is co-delivered to non-immune cells as the site of delivery and also to immune cells which infiltrate the site of delivery. The responses of these two cell types to the same delivered RNA lead to two different effects, which interact to produce a strong immune response against the immunogen. The non-immune cells translate the RNA and express the immunogen. Infiltrating immune cells respond to the RNA by expressing type I interferons and pro-inflammatory cytokines which produce a local adjuvant effect which acts on the immunogen-expressing non-immune cells to upregulate major histocompatibility complex expression, thereby increasing presentation of the translated protein to T cells. The effects on the immune and non-immune cells can be achieved by a single delivery of a single RNA e.g., by a single injection.

Disclosed herein are methods for treating cancer in a human subject comprising administering a recombinant polypeptide comprising a cancer-specific CD8 + T cell epitope. Peptides recognized by major histocompatibility complex (MHC) molecules can activate a T-cell immune response to a target cancer cell in a subject. The present disclosure also provides cancer-specific CD8 + T cell epitopes restricted to MHC molecules expressed by a specific HLA-allele in a subject. The present disclosure also provides compositions encoding recombinant polypeptides that are capable of eliciting swollen memory CD8 + T cell responses.

An immunogenicity prediction model training method includes constructing an immunogenicity prediction model that includes a binding prediction sub-model, a presentation prediction sub-model, and an immunogenicity prediction sub-model, the binding prediction sub-model being configured to predict binding between an epitope and a major histocompatibility complex (MHC), the presentation prediction sub-model being configured to predict cell membrane presentation of an antigenic peptide-major histocompatibility complex (pMHC) molecular complex, and the immunogenicity prediction sub-model being configured to predict immunogenicity of the pMHC; inputting a first sample pair into the immunogenicity prediction model to obtain a sample immunogenicity prediction result, the first sample pair including a first sample epitope sequence and a first sample MHC sequence, and the first sample pair being provided with a first sample immunogenicity label; and training the immunogenicity prediction model with the first sample immunogenicity label as a supervisor of the sample immunogenicity prediction result.

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.

The present invention provides a multispecific molecule capable of binding to an antigen-specific T cell receptor (TCR) expressed on the surface of a cell, the multispecific molecule comprising a first molecule and a second molecule, the first molecule being a polypeptide comprising (i) a peptide (p) presented in the context of a major histocompatibility complex (MHC) molecule (pMHC complex), and (ii) a first multimerization domain, and the second molecule being a polypeptide comprising (i) a domain that specifically binds to a molecule expressed on the surface of a cell expressing the TCR, and (ii) a second multimerization domain, as well as the use of such a molecule for modulating T cell activity and treating diseases such as cancer, infectious diseases, and autoimmune disorders.