94 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.

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.

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 advanced methods for reducing viability of cancer cells and treating cancer, as well as preventing an increase of volume of a tumor present in a body of a living subject, are disclosed. The systems and methods involve application of an alternating field concurrently with administration of at least one composition that inhibits at least one of immunomodulatory cytokine such as (but not limited to) macrophage migration inhibitory factor (MIF), MHC class I chain‐related polypeptide A (MICA), and / or MHC class I chain‐related polypeptide B (MICB).

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 invention discloses a mouse 4T1 breast cancer therapeutic tumor neoantigen mRNA vaccine and a preparation method and application thereof.The breast cancer therapeutic tumor neoantigen mRNA vaccine comprises an antigen epitope composition, the antigen epitope composition comprises at least one of seven polypeptide fragments combined with MHC class I molecules and three polypeptide fragments combined with MHC class II molecules, and the antigen epitope composition comprises at least one of three polypeptide fragments combined with MHC class II molecules; the amino acid sequences of the seven polypeptide fragments combined with the MHC class I molecules are respectively shown as SEQ ID NO.1-SEQ ID NO.7, and the amino acid sequences of the three polypeptide fragments combined with the MHC class II molecules are respectively shown as SEQ ID NO.8-SEQ ID NO.10. The invention further discloses a preparation method of the polypeptide fragments combined with the MHC class I molecules. The vaccine has an obvious inhibition effect on tumor growth.

The present invention relates to the technical field of molecular immunology, and specifically discloses novel antigen polypeptides for lung cancer and their applications. The polypeptide comprises one or more amino acid sequences selected from those shown in, for example, PDGPPEKP (SEQ ID NO.1), MNKALLPAK (SEQ ID NO.2), and MYCELPDSF (SEQ ID NO.3); or is a polypeptide with the same or similar function obtained by substituting and / or deleting and / or adding at least one amino acid in the amino acid sequences of the above polypeptides. The novel antigen polypeptide for lung cancer provided by the present invention can bind to MHC class I molecules on human cells, can significantly stimulate the activation and expansion of T lymphocytes with tumor cell killing effects, and increase the killing ability of T cells against lung cancer cells. Therefore, the polypeptide can be used to prepare drugs for treating lung cancer, especially for preparing lung cancer cell vaccines. The antigen polypeptide can be used to treat lung cancer and prevent recurrence and metastasis in patients after surgery.

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.

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

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

Provided are functional modified stem cell-derived beta (β) cells (SC-beta cells) containing one or more modifications, such as genetic modifications, and related methods of their use and generation. In some embodiments, the modified cells are hypoimmunogenic cells. In some embodiments, the modified SC-beta cells are cells differentiated in vitro from a modified or hypoimmunogenic pluripotent stem cell that contains the one or more modifications. In some embodiments, the one or more modifications reduce or eliminate expression of MHC class I and / or MHC class II human leukocyte antigens and also exogenously express one or more tolerogenic factors such as CD47.

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.

The present disclosure provides a modified cytotoxic T cell (mCTL) wherein the mCTL comprises: a) one or more nucleic acids comprising a nucleotide sequence encoding a T cell receptor (TCR) having specificity for an MHC class I polypeptide presenting a human papilloma virus (HPV) E7 peptide comprising the amino acid sequence YMLDLQPETT (SEQ ID NO: 1) or YMLDLQPET (SEQ ID NO: 2); and b) one or more nucleic acids comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises an antigen binding domain specific for a cancer-associated antigen. The present disclosure provides a method of producing the mCTL. The present disclosure provides a method of treating cancer comprising administering the mCTL to an individual in need thereof.

Compositions, systems, and advanced methods for reducing viability of cancer cells and treating cancer, as well as preventing an increase of volume of a tumor present in a body of a living subject, are disclosed. The systems and methods involve application of an alternating field concurrently with administration of at least one composition that inhibits at least one of immunomodulatory cytokine such as (but not limited to) macrophage migration inhibitory factor (MIF), MHC class I chain-related polypeptide A (MICA), and / or MHC class I chain-related polypeptide B (MICB).

The present invention relates to the technical field of neoantigen screening, and specifically discloses a method for screening neoantigen polypeptide sequences of malignant solid tumors. The method comprises the following steps: obtaining neoantigen prediction results based on HLA class I molecule binding; screening to obtain candidate neoantigen-related mutations; extracting corresponding polypeptide sequences from the neoantigen prediction results to obtain a set of MHC class I potential neoantigen polypeptides; generating all 15-mer sequences centered on the mutation sites and predicting their binding ability to MHC class II molecules to obtain a set of MHC class II potential neoantigen polypeptide sequences; using the maximum margin extension algorithm to obtain long peptide sequences; synthesizing the polypeptide sequences to obtain candidate polypeptide sequences; and evaluating the immunogenicity of the candidate polypeptide sequences to obtain neoantigen polypeptide sequences. The present invention simultaneously considers the binding characteristics of both MHC class I and class II molecules, and can effectively improve the efficiency and accuracy of neoantigen screening.

This invention relates to ligand exchange proteins comprising the luminal domain of TAP-binding protein-related (TAPBPR), which functions as a MHC class I ligand-exchange catalyst when presented to mammalian cells either as a soluble extracellular protein or as a membrane bound cell surface protein. This may be useful in modulating immune responses, including for example loading immunogenic ligand onto tumors or other disease cells to induce their recognition by T cells. Ligand-exchange proteins and methods for their use are provided. The invention further relates to an approach for generating conditional peptide ligands for a range of disease-related MHC-I allotypes. The present invention relates to chicken and human TAPBPRs and tapasins as well as orthologs thereof, derivatives thereof, and any mutants thereof as well as any combinations thereof. The present invention also relates to placeholder conditional ligands for ligand-exchange reactions across multiple HLA allotypes.

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 present invention relates to an H LA tumor antigen polypeptide comprising a cell-penetrating peptide (HTAPP-CPP) use as a medicament in the therapeutic and prophylactic treatment of carcinomas. The HLA tumor antigen polypeptide comprises a cell-penetrating peptide (HTAPP-CPP) and further comprises HLA tumor antigen peptides (HTAP) associated with MHC class I and / or class II complexes, arranged on at least one HLA tumor antigen polypeptide (HTAPP). These HTAP are tumor-specific or tumor-associated. The HLA tumor antigen polypeptide (HTAPP) is provided as a tandem polypeptide or an overlapping tandem polypeptide, both comprising at least 2 HLA tumor antigen peptides corresponding to MHC class I and / or class II complexes. This invention further comprises a method for determining an pharmaceutical composition comprising HLA tumor antigen polypeptide(s), a method for preparing a formulation according to the invention, and the use of a composition and formulation according to the invention for the preparation of a pharmaceutical composition.

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.

The present invention provides compositions and methods for isolating, manipulating mammalian MHC class I restrictive antigen-specific regulatory T cells, and for therapeutic and other purposes. The regulatory T cells may be characterized as CD8 + cells that specifically inhibit the response of autoreactive and / or pathogenic CD4 + T cells by cytotoxic mechanisms, including but not limited to Perforin, other components of the Perforin / granzyme apoptosis pathway, and the like. The regulatory T cells have antigen specificity but are not activated by the same antigen as the autoreactive and / or pathogenic CD4 + T cells. In a human body, the regulatory T cells express an inhibitory KIR protein, such as one or more of KIR2DL2, KIR2DL3, and KIR3DL1.