27 results about "Major histocompatibility complex" patented technology

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).

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 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.

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.

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 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.

Disclosed are methods for treating a cancer and / or modulating immune CD4+ T cell mediated therapies comprising administering to a subject a fucose. In one aspect, disclosed herein are methods of modulating major histocompatibility complex II human lymphocyte antigen (HLA)-DRB 1 expression on the surface of a cell comprising contacting the cell with an agent that modulates the amount of fucosylation on the cell; wherein an increase in fucosylation increases surface expression of HLA-DRB 1; and wherein a decrease in fucosylation decreases the surface expression of HLA-DRB 1.

Provided is an HLA-independent T cell receptor. This major histocompatibility complex class I-related molecule 1 (MR1)-restricted T cell receptor (TCR) comprises a TCRα chain that includes a CDR3 having a specific amino acid sequence and is encoded by a specific nucleotide sequence and a TCRβ chain that includes a CDR3 having a specific amino acid sequence and is encoded by a specific nucleotide sequence. This TCR specifically recognizes an antigen expressed in breast cancer cells.

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

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

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

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

The present invention concerns antigen binding proteins directed against PRAME protein-derived antigens. The invention in particular provides antigen binding proteins which are specific for the tumor expressed antigen PRAME, wherein the tumor antigen comprises or consists of SEQ ID NO: 50 and is in a complex with a major histocompatibility complex (MHC) protein. The antigen binding proteins of the invention contain, in particular, the complementary determining regions (CDRs) of novel engineered T cell receptors (TCRs) that specifically bind to said PRAME peptide. The antigen binding proteins of the invention are for use in the diagnosis, treatment and prevention of PRAME expressing cancerous diseases. Further provided are nucleic acids encoding the antigen binding proteins of the invention, vectors comprising said nucleic acids, recombinant cells expressing the antigen binding proteins and pharmaceutical compositions comprising the antigen binding proteins of the invention.

The purpose of the present invention is to provide a means for selecting subject-derived neoantigens. The above problem is solved by providing a method for selecting a subject-derived neoantigen, said method comprising: a step of acquiring sequence data of a normal cell and a cancer cell derived from a subject, a step of identifying a gene having a genetic mutation specific to the cancer cell, and a step of identifying a peptide based on a wild-type gene corresponding to the gene having the genetic mutation specific to the cancer cell from a major histocompatibility complex (MHC)-presented peptide database, wherein the genetic mutation is a missense mutation, and the peptide based on the wild-type gene corresponding to the gene having the genetic mutation has a wild-type amino acid corresponding to the position of an amino acid mutation due to the genetic mutation.

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.

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.

Described herein is a fluorescent nanocomposite. The fluorescent nanocomposite structure may include a plasmonic nanostructure comprising having at least one localized surface plasmon resonance wavelength (λLSPR), at least one spacer coating, at least one fluorescent agent having a maximum excitation wavelength (λEX), and at least one peptide-loaded major histocompatibility complex (MHC) molecule (pMHC). The fluorescent nanocomposite structure has a fluorescent intensity that is at least 500 times greater than a fluorescent intensity of the at least one fluorescent agent alone.

Disclosed herein are methods of inhibiting an interaction of a T cell receptor with a peptide-major histocompatibility complex comprising administering inhibitory peptides that bind to the T cell receptor without the aid of a major histocompatibility complex to inhibit the interaction, and methods of identifying the inhibitory peptides.

Described herein is a fluorescent nanocomposite. The fluorescent nanocomposite structure may include a plasmonic nanostructure comprising having at least one localized surface plasmon resonance wavelength (λLSPR), at least one spacer coating, at least one fluorescent agent having a maximum excitation wavelength (λEX), and at least one peptide-loaded major histocompatibility complex (MHC) molecule (pMHC). The fluorescent nanocomposite structure has a fluorescent intensity that is at least 500 times greater than a fluorescent intensity of the at least one fluorescent agent alone.

The present invention relates to a vaccine composition for cancer prevention or treatment comprising an antigen-presenting cell in which a complex of MHC (major histocompatibility complex) and a tumor antigen is overexpressed on the cell surface, and to cancer treatment using the same.