44 results about "MHC class I" patented technology

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3

Compositions, systems, and methods are disclosed for reducing the viability of cancer cells and treating cancer, as well as preventing an increase in volume of a tumor present in the body of a living subject. The systems and methods involve applying an alternating field while administering at least one composition that increases the expression of MHC class I molecules in cancer cells.

The present invention relates to artificial antigen presenting cell (aAPC) scaffolds to provide cells with specific functional stimulation to obtain phenotypic and functional properties ideal to mediate tumor regression or viral clearance. In particular, the scaffolds of the present invention comprise stabilized MHC class I molecules free of antigenic peptide. The scaffolds can be loaded with antigenic peptide on demand, providing an agile platform for effective expansion and functional stimulation of specific T cells in a peptide-MHC-directed fashion.

The invention relates to recombinant polynucleotides encoding at least a recombinant polynucleotide expressing at least a first fusion polypeptide that comprises MHC class I T-cell epitopes suitable to elicit a T cell immune response in a host in need thereof, wherein the MHC class I T-cell epitopes originate from a plurality of antigens wherein the antigens comprise at least non-structural antigens and are from at least one flavivirus selected from the group of 10 Dengue virus (DENV), ZIKA virus (ZIKV) and Yellow Fever virus (YFV). The invention also relates to the polypeptides comprising polyepitopes of said antigens encoded by the recombinant polynucleotides.

The present invention relates to a pharmaceutical composition to prevent or treat viral infection(s), particularly to a combination agent / composition comprising of at least two and most particularly up to 12 different antigen polypeptides corresponding to HLA antigen peptides matching viral epitopes, for immunization against at least one, preferably two, particularly preferably up to 4 viral infectious diseases, a combination preparation (or parts thereof), a method for determining / identifying at least one HLA antigen peptide corresponding to the MHC class I complexes and / or antigen polypeptide for use in the pharmaceutical composition and a method for preparing a pharmaceutical composition comprising at least one antigen polypeptide according to the invention.

A NOD.Cg-Prkdcscid NSG) mouse which is genetically modified such that the NSG mouse lacks functional major histocompatibility complex I (MHC I) and lacks functional major histocompatibility complex II (MHC II) is provided according to aspects of the present invention. According to specific aspects the genetically modified NSG mouse is a NOD.Cg- Prkdcscid H2-K1tml Bpe H2-Ab1em Mvw H2-D1tml H2rg Wjl / SzJ NSG- RIP-DTR (IAnull) mouse, or a NOD.Cg-B2m'm" Une Prkdcscid H2dlAbl-Ea H2rg!"1 Wjl / SzJ (NSG- B2M ull (IA mouse. Human immune cells and / or human tumor cells are administered to a genetically modified immunodeficient mouse according to aspects described herein and assays of one or more test substances can be performed using the provided mice. 20 24 20 47 25 09 J ul 2 02 4 A B S T R A C T 2 0 2 4 2 0 4 7 2 5 0 9 J u l 2 0 2 4

The present invention relates to genetically engineered NK cells and uses thereof. Specifically provided is a host cell comprising a nucleic acid construct comprising (1) a nucleotide sequence encoding a TCR and a CD8a molecule and (2) a nucleotide sequence encoding a CD3 molecule. The cells produced by the present invention have significant cytotoxicity against specific tumor cells and retain the killing effect of NK cells on tumor cells with down-regulated MHC class I molecules.

Disclosed herein are engineered cells and / or hypoimmunogenic cells including engineered cells and / or hypoimmunogenic stem cells, engineered cells and / or hypoimmunogenic cells differentiated therefrom, and / or engineered cells and / or hypoimmunogenic CAR-T cells (primary or differentiated from engineered and / or hypoimmunogenic stem cells) and related methods of their use and generation comprising regulatable reduced expression of one or more MHC class I and / or MHC class II human leukocyte antigen molecules and regulatable overexpression of CD47. Provided herein are cells further exhibiting reduced expression of T-cell receptors.

Provided herein are compositions comprising a liposome comprising RNA molecules and a cationic lipid, wherein the RNA molecules encode at least one MHC Class II epitope of a mutant Histone 3 (H3) protein comprising a K27M mutation and optionally at least one MHC Class I epitope of the mutant H3 protein. In exemplary embodiments, the RNA molecules comprise a sequence of SEQ ID NO: 12 or 14. Methods of increasing central memory T cells, increasing an immune response, or treating a diffuse midline glioma (DMG), in a subject are provided herein. In exemplary embodiments, the methods comprise administering to the subject the compositions provided herein.

The invention discloses a sequence and structure combination-based peptide fragment-MHC class I molecule presentation prediction method, which comprises the following steps of: acquiring a protein data set, and constructing a peptide fragment-MHC class I molecule combination data set and a peptide fragment-MHC class I molecular structure data set; calculating an amino acid frequency matrix according to the molecular combination data set, obtaining a peptide fragment-MHC class I molecular contact diagram according to the molecular structure data set, and constructing a general interaction diagram based on the molecular contact diagram; pre-training a protein characterization model by using the protein data set and performing fine tuning to obtain a fine-tuned protein characterization model, extracting MHC structural features, and extracting sequence features of polypeptide by using a sequence feature extraction model; and inputting the weighted sequence features of the polypeptide and the MHC structural features into a graph neural network model, carrying out feature aggregation through a general interaction graph, and outputting a peptide fragment-MHC class I molecule presentation prediction result. According to the invention, the prediction accuracy is improved.

Compositions and methods are provided for isolating, manipulating and using for therapeutic and other purposes, mammalian, MHC Class I restricted, antigen-specific regulatory T cells. The regulatory T cells can be characterized as CD8+ cells that specifically suppress the responses of self-reactive and / or pathogenic CD4+ T cells by cytotoxic mechanisms including, without limitation, perforin, other components of the perforin / granzyme apoptosis pathway, etc. The regulatory T cells are antigen-specific, but are not activated by the same antigen as the self-reactive and / or pathogenic CD4+ T cells. In humans the regulatory T cells express inhibitory KIR proteins, e.g. one or more of KIR2DL2, KIR2DL3, and KIR3DL1.

The present disclosure provides engineered T cells with reduced expression or knock out of an immunophilin, and which express a chimeric antigen receptor (CAR) and / or comprise one or more modifications that disrupt MHC class I and / or MHC class II alleles and increase expression of a tolerogenic factor. The present disclosure also provides methods of treating a subject having or suspected of having a post-transplant disorder by administering T cells with reduced expression or knock out of an immunophilin. Also disclosed are pharmaceutical compositions comprising T cells with reduced expression of an immunophilin, for use in treating a subject having or suspected of having a post-transplant disorder.

Disclosed herein is a method for predicting MHC class I or MHC class II immunogenicity of tumor-specific neoantigens by both predicting MHC class I or MHC class II binding affinity and predicting the likelihood that the tumor-specific neoantigens will be presented on the cell surface by MHC class I or class II proteins.

The invention provides an MHC class I autoantigen peptide for inducing immune tolerance. The amino acid sequence of the MHC class I autoantigen peptide is shown as SEQ ID NO. 4. The invention also provides a DNA (Deoxyribose Nucleic Acid) molecule for coding the MHC class I autoantigen peptide for inducing immune tolerance. The invention also provides a recombinant vector which contains the DNA molecule. The invention also provides application of the polypeptide in preparation of drugs for preventing or treating autoimmune diseases. The autoantigen peptide provided by the invention is derived from an autoantigen peptide presented on the surface of an activated CD4 + T cell, and can be specifically recognized by a self-reactive CD8 + T cell, so that immune response is induced, and regulation and control on a pathogenic T cell are realized. Through the mechanism, the antigen peptide can be used for inducing immune tolerance of the body, and has application value in improving or treating autoimmune diseases.

Provided herein are methods of administering engineered islet cells, including functionally modified beta cells containing one or more modifications (such as genetic modifications). In some embodiments, the engineered pancreatic islets are low immunogen cells. In some embodiments, the one or more modifications reduce or eliminate the expression of one or more MHC class I and / or MHC class II human leukocyte antigens, while increasing the expression of one or more tolerogenic factors, such as CD47. In some embodiments, the subject has a beta cell related condition, such as diabetes (e.g., type I diabetes).

Herein is reported a complex comprising as first part an antibody derived part that specifically binds to a target antigen, and as second part a virus-derived peptide linked to a MHC class I protein complex. With the complex as reported herein existing virus-specific circulating cytotoxic T-cells (T-memory-cells or T-effector-cells) of an individual can be directed to cells expressing the target antigen, to which the antibody derived part of the covalent complex specifically binds to, by dressing these cells with a MHC class I complexes mimicking an acute viral infection. Thus, one aspect as reported herein is a complex, characterized in that it comprises one fusion polypeptide that comprises in N- to C-terminal direction either (i) a β2-microglobulin, and (ii) the extracellular domains α1, α2, and α3 of a class I MHC molecule with a relative frequency of less than 1 Percent, or (i) a virus- derived peptide, (ii) a β2-microglobulin, and (iii) the extracellular domains alpha1, α2, and α3 of a class I MHC molecule with a relative frequency of 1 Percent or more, and two polypeptide chains, which are linked by one or more disulfide bonds, wherein the first disulfide-linked polypeptide chain comprises in N- to C-terminal direction (i) an immunoglobulin light or heavy chain variable domain, (ii) an immunoglobulin light or heavy chain constant domain, and (iii) an antibody heavy chain hinge region polypeptide, and the second disulfide-linked polypeptide chain comprises an antibody heavy chain hinge region polypeptide, wherein the fusion polypeptide is either covalently bound either to the C-terminus or the N-terminus of one of the disulfide-linked polypeptide chains, or covalently bound to the Nterminus of an antibody variable domain that is the complementary heavy or light chain variable domain to that comprised in the first disulfidelinked polypeptide chain.

Disclosed herein are methods for predicting tumor-specific neoantigen MHC class I or MHC class II immunogenicity by jointly predicting MHC class I or MHC class II binding affinity and predicting the likelihood a tumor-specific neoantigen will be presented by a MHC class I or class II protein on a cell-surface.

The present invention relates to two tissue MHC class I immune peptide profiles that are dedicated to the preparation of anti-cancer vaccines against non-small cell lung cancer (NSCLC) and to the identification and isolation of human NSCLC-specific T cells by an antibody-free method defined using a list of 25 quantitative peptides, the 25 quantitative peptides are up-regulated or down-regulated in tumor tissue of an NSCLC patient to healthy tissue at the time of comparison of healthy tissue to a matched NSCLC patient-derived tissue sample. Therefore, the invention has important significance for understanding basic and application biological problems.

The present disclosure relates to the treatment of cancer. In particular, the present disclosure provides novel therapeutic antibodies that target MHC class I chain-associated protein A (MICA) in a manner that reduces the ability of tumor cells to escape immune clearance mediated by natural killer cell group 2D (NKG2D) receptors.

This paper describes a composition and a method for using the same.The composition described herein can comprise a single-chain trimeric nucleic acid encoding a first T cell epitope, β2 microglobulin, and an MHC class I heavy chain sequence.The method described herein can be used to activate and / or expand antigen-presenting cells.The method described herein can also be used to treat or prevent viral infection, bacterial infection, parasitic infection, and / or cancer in subjects.

This invention relates to a method for screening extracellular tissue peptides in mammalian tissue samples for health status assessment, disease diagnosis, and discovery of nascent antigens. The invention includes the preparation and analysis of tissue samples from solid tumors and focuses on extracellular peptidomics and major histocompatibility complex (MHC) class I immunopeptidomics. This method is antibody-free and utilizes amino acid sequencing and tandem mass spectrometry. It is a simple, inexpensive, and rapid method for comprehensively profiling solid tumor peptidomics (extracellular peptidomics and MHC class I immunopeptidomics). This method may be used for screening and as a biomarker for health status assessment, disease diagnosis, discovery of nascent antigens, and prognosis prediction in salivary gland tumors. Furthermore, tissue MHC class I immunopeptidomics can also be applied to the discovery of nascent antigens, vaccine development, and design of immunotherapies.

Provided herein are methods of increasing the immunogenicity of mammalian cells, methods of producing antigen presenting cells to stimulate an immune response in a subject, and methods of stimulating an immune response in a subject in need thereof. The methods comprise providing mammalian cells, antigen presenting cells, or the subject with an immunogenic agent and a TAP-binding protein-related (TAPBPR) polypeptide comprising an amino sequence having at least 90% identity to SEQ ID NO:7. wherein the TAPBPR polypeptide loads the immunogenic agent onto the surface MHC class I molecules thereby increasing the immunogenicity of the mammalian cells, producing antigen presenting cells to stimulate an immune response, and stimulating an immune response in a subject.

The invention provides a method of producing a non-immunogenic (bio)engineered tissue from pluripotent stem cells or pluripotent stem cell derivatives, the respective cells being deficient of MHC class I molecules and comprising an immunomodulatory protein on their surface, wherein the method comprises inducing the differentiation of the pluripotent stem cells into a cell type that is essential for the function of the engineered tissue under conditions that also allow the formation of the engineered tissue, thereby rendering the engineered tissue to be non-immunogenic to a recipient of the engineered tissue. The present invention further relates to an engineered tissue, a pharmaceutical composition comprising the engineered tissue, medical treatments using the engineered tissue and uses of the engineered tissue.

Provided herein are methods of dosing engineered islet cells that include functional modified beta cell containing one or more modifications, such as genetic modifications. In some embodiments, the engineered islets are hypoimmunogenic cells. In some embodiments, the one or more modifications reduce or eliminate expression of one or more MHC class I and / or MHC class II human leukocyte antigens and also increase expression of one or more tolerogenic factors, such as CD47. In some embodiments, the subject has a beta cell related disorder, such as diabetes (e.g. Type I diabetes).

This disclosure provides compositions and methods for T-cell mediated depletion of B cells. The compositions and methods may be used, for example, for the treatment of autoimmune disorders, immune-mediated inflammation disorders and other B-cell mediated immune disorders. In embodiments, the depletion is effected by methods comprising administering to an individual a T cell engaging protein ("TEP"), wherein the TEP comprises: (i) a peptide-major histocompatibility complex ("pMHC") comprising a peptide epitope, a β2-microglobulin ("β2M") polypeptide, and an MHC class I heavy chain polypeptide; (ii) an immunoglobulin ("Ig") Fc polypeptide; (iii) at least one B-cell targeting component; and (iv) optionally one or more activating immunomodulatory polypeptides, wherein each of the at least one B-cell targeting components of the TEP binds to a B cell binding partner on a B cell, a plasmablast, and / or a plasma cell.

The application relates to the field of biomaterials, and particularly relates to application of a giant salamander mucus extract hydrolysate in preparation of an anti-dentin sensitivity agent. The anti-dentin sensitivity agent comprises a hydrolysate retaining the biological activity of SSAD, the hydrolysate being a product of reduction of the giant salamander mucus extract by an acid solution with a pH value of 1-5, and the product comprising five active proteins, namely MHC class I molecule alpha chain, homeobox protein Hox-D13, abnormal heavy chain 3 of axonemal dynein, ATP synthase protein and cytochrome b; the particle size of the giant salamander mucus extract is 1-50 mu m; and the pH value of the anti-dentin sensitivity agent is 5.5-7.5. The giant salamander mucus extract is treated by the acid solution to obtain the hydrolysate containing the multiple active proteins, the hydrolysate can effectively promote deep closure of dentin tubules, and has long-term stable biocompatibility; the pH value is controlled to ensure that the biological activity is completely retained, and the curative effect of the anti-dentin sensitivity agent is remarkably improved.

Provided herein are methods of producing engineered target organs (e.g., a pancreas) and / or cells therefrom (e.g., islets) using a non-human mammal host. In some embodiments, the methods relate to injecting hypoimmunogenic human pluripotent stem cells (HIP-hPSC) into a blastocyst of a surrogate non-human mammal to produce a chimeric blastocyst and implanting the chimeric blastocyst into the uterus of the surrogate non-human mammal, wherein after implantation the chimeric blastocyst develops into a non-human mammal host comprising a target organ with chimeric contribution from the HIP-hPSCs. In further embodiments, the target organ and / or cells therefrom are transplanted into a human subject having a disease or condition. In some embodiments, the HIP-hPSCs comprise one or more modifications that reduce or eliminate expression of one or more MHC class I and / or MHC class II human leukocyte antigens and also increase expression of one or more tolerogenic factors.

Disclosed herein are engineered cells and / or hypoimmunogenic cells including engineered and / or hypoimmunogenic stem cells, engineered and / or hypoimmunogenic cells differentiated therefrom, engineered and / or hypoimmunogenic CAR-T cells (primary or differentiated from engineered and / or hypoimmunogenic stem cells) and related methods of their use and generation. Provided herein are engineered and / or hypoimmunogenic cells exhibiting reduced expression of MHC class I and / or MHC class II human leukocyte antigens and T-cell receptors. In some embodiments, such cells also exogenously express one or more tolerogenic factors such as CD47 and one or more chimeric antigen receptors (CAR)s.

The present invention relates to a method of screening extracellular tissue peptides in mammalian tissue samples for health status evaluation, disease diagnosis and neoantigen discovery. The present invention relates to the preparation and analysis of tissue samples from solid tumors focused on extracellular peptidomics and tissue major histocompatibility complex (MHC) class I immunopeptidomics. The method does not need an antibody, and amino acid sequencing is carried out by tandem mass spectrometry. The method is simple, convenient, economical and rapid, and can comprehensively characterize solid tumor peptiomics (extracellular peptide group and MHC class I immune peptiomics). The method has the potential of screening and serving as a biomarker for health status evaluation, disease diagnosis, neoantigen discovery and prognosis of salivary gland tumors. In addition, tissue MHC class I immunopeptidomics methods are used for neoantigen discovery, vaccine development and immunotherapy design.