60 results about "MHC class I" patented technology

This disclosure relates methods for expanding γδ T cells. More specifically, the disclosure relates to methods of expanding γδ T cells that have an eliminated or reduced expression of endogenous MHC Class I molecules, by expressing a single-chain fusion HLA Class I protein. In some embodiments, the endogenous B2M gene of the γδ T cells is disrupted. In some embodiments, the single-chain fusion HLA Class I protein includes at least a portion of B2M protein and at least a portion of HLA-E heavy chain.

Provided is a composition for treating cancer in a subject, the composition containing: a nucleic acid which encodes a peptide that includes at least one non-self MHC Class I restricted epitope and at least one non-self MHC Class II restricted epitope; or cells which express the peptide. Also provided is a method comprising analyzing a gene for a cancer tissue obtained from a subject, and determining whether or not a non-self antigen peptide that comprises a non-self amino acid sequence having a longer length than a cut-off value is present in the cancer tissue.

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.

To provide a cell including a cell expressing CD24, and related method of use and creation thereof.SOLUTION: Provided is an isolated cell including modification for increasing reduced expression of MHC class I and / or MHC class II human leukocyte antigens and expression of CD24 in a cell. In some embodiments, the cell includes reduced expression of MHC class I and MHC class II human leukocyte antigens.SELECTED DRAWING: None

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.

The present disclosure relates to the field of adoptive immune cells, and particularly relates to recombinant nucleic acids encoding molecules to reduce TCR-CD3 complex expression, MHC class I and class II expression, and CD58 expression on immune cells, the use of such nucleic acid molecules and compositions for production of allogeneic immune cells, and pharmaceutical compositions containing the allogeneic immune cells. Also provided are methods for treating cancer.

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.

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 disclosure provides immunodeficient NOD.Cg-Prkdc scid Il2rg tm1Wjl / SzJ (NSG TM ) mouse models comprising an inactivated mouse Flt3 allele, a nucleic acid encoding human interleukin 3 (IL3), a nucleic acid encoding human granulocyte / macrophage stimulating factor (GM-CSF), a nucleic acid encoding human stem cell factor (SCF), and an HLA-A2 / H2-D / B2M transgene encoding (i) human B2 microglobulin (B2M) covalently linked to the MHC class I, alpha 1 and alpha 2 binding domains of the human HLA-A2.1 gene and (ii) the alpha 3 cytoplasmic and transmembrane domains of murine H2-Db.

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.

Provided herein are engineered MHC molecules compositions for treatment of a disease or disorder. The compositions described herein include an engineered MHC heavy chain; an engineered beta 2-microglobulin (B2m) protein; and / or an MHC class I molecule complex that have been modified to have increased binding affinity to cell coreceptors, such as CD8, and also have increased internalization in immune cells relative to an otherwise comparable MHC class I heavy chain, B2m protein, or MHC class I molecule complex. Various protein constructs and pharmaceutical compositions of the engineered MHC molecules are provided. Methods of utilizing the protein constructs and pharmaceutical compositions of the modified MHC molecules are also provided.

Disclosed is a method for identifying peptides, which are bound and / or presented by MHC class I and / or MHC class II molecules in an individual, where the method utilises a transformer encoder-decoder model comprising an artificial neural network (ANN) architecture, wherein the transformer encoder receives as input MHC molecule amino acid sequence of a peptide:MHC data pair and outputs a high-dimensional representation of the MHC amino acid sequence, wherein the transformer decoder receives the high-dimensional representation of the MHC molecule amino acid sequence and the peptide amino acid sequence of a peptide:MHC data pair with residue embedding and positional encoding as input and outputs a high-dimensional representation of the relationship between the MHC molecule amino acid sequence and the peptide sequence, and wherein the output from the transformer decoder is used to calculate a quantitative assessment of the ability of the MHC molecule to bind and / or present the peptide. Also disclosed is a method of training the model, a computer or computer system adapted to carry out the method, and a method of identifying MHC binding amino acid sequence derived from proteins.

The present invention relates to a pharmaceutical composition for the treatment or prevention of breast cancer / mammary carcinoma, in particular locally recurrent or metastatic breast cancer, in a patient or patient group suffering from or suspected of suffering from breast cancer, comprising: at least 4 to 8 HLA-A tumor antigen peptides corresponding to MHC class I complexes and at least 2 tumor antigen peptides corresponding to MHC class II complexes, wherein the HLA tumor antigen peptides are tumor specific or tumor associated HLA antigen peptides and are directed against at least one MHC complex, including combinations thereof; a pharmaceutical composition, a kit (or parts thereof); a method for determining class I and / or class II HLA peptides; a method for the manufacture of a pharmaceutical composition according to the invention; and the use of a pharmaceutical composition according to the invention for the manufacture of a pharmaceutical composition for the treatment of malignancies, leukemias and tumors.

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 comprising a heavy chain comprising an alpha-1 domain and an alpha-2 domain connected by a disulfide bridge, wherein said MHC class I molecules are 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.

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.

Compositions and methods of use thereof are described herein. The compositions described herein may comprise a single-stranded trimeric nucleic acid encoding a first T cell epitope, a beta2-microglobulin, and an MHC class I heavy chain sequence. The methods described herein can be used to activate and / or expand antigen presenting cells. The methods described herein may also be used to treat or prevent viral infections, bacterial infections, parasitic infections, and / or cancer in a subject.

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.