53 results about "Leucocyte antigens" patented technology

The present invention relates to chimeric antigen receptors (CAR) against multiple but not all human leukocyte antigen (HLA-G) isoforms. More specifically, the invention concerns CARs that are specific for HLA-G β2M-free or β2M-associated immunosuppressive isoforms respectively.

The invention relates to the technical field of biomedical detection, in particular to a genetic typing primer group, a kit and a genetic typing method for accurately realizing an ultrahigh resolution level of 11 sites of human leukocyte antigen (HLA) based on a nanopore sequencing technology. According to the genetic typing primer group for the HLA ultrahigh resolution level, the primer group is used for HLA gene multiple amplification, and the primer group comprises an HLA-A site primer pair, an HLA-B site primer pair, an HLA-C site primer pair, an HLA-DRB1 site primer pair, an HLA-DRB3 / 4 / 5 site primer pair, an HLA-DQA1 site primer pair, an HLA-DQB1 site primer pair, an HLA-DPA1 site primer pair and an HLA-DPB1 site primer pair. According to the primer group for multiple amplification of 11 genes for HLA typing, disclosed by the invention, the amplification of each gene can be simultaneously carried out on the loci of HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 of the HLA genes in a reaction system, so that the integrity, the amplification efficiency and the amplification uniformity of the gene amplification as well as the accuracy of subsequent HLA gene typing are improved.

The invention relates to a tumor neoantigen prediction method and a tumor neoantigen prediction system. The method comprises the following steps: acquiring a plurality of amino acid sequences in a gene of a person to be tested as a plurality of test peptides to be compared with a plurality of human protein sequences in a protein sequence database so as to find out a plurality of similar peptides matched with the human protein sequences; filtering similar peptides from the test peptides, and respectively inputting the filtered test peptides into a plurality of trained human leukocyte antigen models to obtain a plurality of sequencing results of the test peptides; calculating the weighted sum of the sequencing of each test peptide in the sequencing result as the score of the test peptide; and selecting at least one of the test peptides as a neoantigen suitable for the subject according to the fraction.

The present invention relates to an antibody that specifically binds to human leukocyte antigen G (HLA-G), or an antigen binding fragment thereof, and a use thereof, and more particularly, to an antibody that specifically binds to human leukocyte antigen G (HLA-G), or an antigen binding fragment thereof, and a use thereof. The antibody specifically binding to HLA-G or the antigen-binding fragment thereof inhibits interaction between HLA-G and ILT-2 while specifically binding to HLA-G, and thus can exhibit excellent anticancer effects such as inhibition of tumor growth.

The present invention relates to an in vitro method for preparing an immunoreactive agent against human cancer cells infected with an HPV16-associated virus, said method comprising expressing at least part of a nucleic acid sequence encoding an immunoreactive agent obtained from an immune cell stimulated by a complex comprising a human leukocyte antigen (HLA) and a stimulating peptide (stimulating complex), wherein the stimulating peptide (i) consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 1 and SEQ ID NO: 2, and the HLA is from an HLA supertype HLA-A01; (ii) consists of an amino acid sequence of SEQ ID NO: 11, and the HLA is from an HLA supertype HLA-A02; (iii) consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 34 to SEQ ID NO: 37, and the HLA is from an HLA supertype HLA-A03 / A11; (iv) consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 60 and SEQ ID NO: 61, and the HLA is from an HLA supertype HLA-A24; (v) consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 61, SEQ ID NO: 76 and SEQ ID NO: 77, and the HLA is from an HLA supertype HLA-B07; or (vi) consists of an amino acid sequence selected from the group consisting of SEQ ID NO: 61 and SEQ ID NO: 85 to SEQ ID NO: 92, and the HLA is from an HLA supertype HLA-B15; and wherein HPV16-derived peptides consisting of the same amino acid sequence as the stimulating peptides have been demonstrated to be presented by human HPV16-positive cancer cells, and methods and uses related thereto.

The present disclosure provides an engineered population of natural killer cells wherein the NK cells express at least one polypeptide selected from the group consisting of human leukocyte antigen E, human leukocyte antigen F, and human leukocyte antigen G. The NK cell comprises a genetically modified disruption of one or more copies of an endogenous beta-2 microglobulin and a genetically modified disruption of one or more copies of a human leukocyte antigen class II-related gene, the human leukocyte antigen class II-related gene is selected from a protein containing regulatory factor X-related ankyrin, a regulatory factor 5, a regulatory factor X-related protein and a class II trans-activator. Also provided are a method of producing human pluripotent stem cell-derived engineered natural killer cells without feeder cells, and a method of treating a disease or condition in a subject by administering the NK cells to the subject.

Chimeric antigen receptors (CARs) that bind to Human Leukocyte Antigen (HLA)-pan DP, cells that comprise the CARS and methods of making and using the cells are provided.

The present disclosure provides modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising chimeric antigen receptors (CARs) specific for CD45. In certain embodiments, the modified immune cells or precursors thereof further comprise or instead comprise a modified endogenous gene locus encoding CD45.

The invention provides binding proteins capable of specific binding to a human leukocyte antigen (HLA) complex type A2 presenting a peptide having the amino acid sequence ALYDKTKRI set forth in SEQ ID NO: 1 (peptide T1) or the amino acid sequence ALYDKTKRIFL set forth in SEQ ID NO: 15 (peptide T3) derived from human terminal deoxynucleotidyl transferase (TdT). The binding proteins comprise an antigen binding unit comprising an α-chain variable domain and a β-chain variable domain each comprising 3 complementarity determining regions (CDRs) derived from TCRs that recognise the peptides. The binding proteins and cells expressing them, may be used in cancer therapy.

The invention provides therapeutic cells that are comprehensively immune protected having a reduced or eliminated surface leukocyte antigen class I, an enhanced SIRPa engager (SIRPaE) expression, and an enhanced Fc sequestration molecule expression. In some aspects, the cells of the invention engage one or both of CD200R or CD99 ligands on immune cells. In other aspects, the cells of the invention sequester antibodies to inhibit humoral immunity. In other aspects, the cells of the invention have reduced or eliminated leukocyte antigens from both class I and class II. In other embodiments, the cells of the invention are ABO or Rh compatible with a recipient subject. In other embodiments, the cells of the invention are allogeneic or xenogeneic to the recipient.

The present disclosure relates to bicistronic polypeptide constructs for use in allogeneic gene therapy, such as CAR-T cell therapy. The bicistronic constructs comprise a first polynucleotide encoding a therapeutic molecule (e.g., CAR-T or an antibody) and a second polynucleotide encoding an immune surveillance masking molecule (ISMM). The ISMs comprise a human leukocyte antigen-E genetically fused to a non-functional form, such as a fragment, of a protein, such as beta-2 microglobulin or B2M, which is knocked out by insertion of the bicistronic construct. Also provided are vectors, cells (e.g., CAR-T cells) comprising the bicistronic constructs and methods of use. Kits and articles of manufacture are also provided. The present disclosure also provides four new insertion sites that can be used to insert an expression construct into the B2M gene.

Provided herein are genetically modified cells, such as universal donor cells, that are compatible with multiple subjects; and methods of producing such genetically modified cells. These universal donor cells comprise at least one genetic modification within or near at least one gene encoding one or more MHC-I or MHC-II human leukocyte antigens or components of the MHC-I or MHC-II complex or transcriptional regulators, at least one genetic modification that increases the expression of at least one polynucleotide encoding a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene encoding a survival factor.

Development of de novo donor specific antibodies (dnDSA) and antibody mediated rejection (AMR) remain to be a barrier for long term graft and patient survival. Most dnDSA are against mismatched donor HLA-DQ antigens. New methods for evaluating HLA-DQ mismatches are provided based on assessment of compositions and locations of categorical amino acid mismatched epitope (CAME). Specifically, amino acid residues of the HLA-DQ protein can be categorized into four groups, and categorical mismatched peptides are ranked in terms of likelihood of presentation by the recipient HLA-DRB1. Applicant has discovered the presence of DQB1 mismatches with %Ranking score ≤1 (corresponding to a binding strength between mismatched DQB1 and DQR1 between donor and recipient being in top 1%) is associated with development of dnDSA in heart transplant recipients, and dnDSA increases the risk of AMR only in recipients who have DQ mismatches with %Ranking score ≤ 1.

Chimeric antigen receptors (CARs) that bind to Human Leukocyte Antigen (HLA)-pan DP, cells that comprise the CARS and methods of making and using the cells are provided.

Compounds that modulate the function, activity and / or expression of porcine leukocyte antigen complex II (SLA II) genes and / or SLA II proteins, use for medicine, use as medicaments or use for the treatment or prevention of ASF or ASFV infection are disclosed. The present disclosure also provides the use of the SLA-DMA, SLA-DMB, RFXANK, RFXAP5, and CIITA genes to achieve ASFV resistance.

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.

A method of detecting the risk of biofilm development comprising: taking a blood sample from a patient; analysing the blood sample by performing human leukocyte antigen (HLA) genotyping; determining i

Methods for providing a vaccine composition capable of effectively inducing a systemic immune response and / or a topical immune response upon administration wherein the composition comprises a human leukocyte antigen class I (HLAI) restrictive epitope selected from the viral pathogen non-virion constituent protein (non-VIP) and thus elicits a CD8T cell response specific against viral infected cells.

A method for providing a vaccine composition capable of effectively inducing a systemic immune response and / or a local immune response upon administration, wherein the composition comprises a human leukocyte antigen class I (HLA I)-restricted epitope selected from viral pathogen non-viral particle constituent proteins (non-VIPs), and thus elicits a CD8 T cell response specific for virus-infected cells.

Provided herein, inter alia, are recombinant proteins including a human leukocyte antigen (HLA) heavy chain binding peptide, a beta-2 microglobulin (B2M) sequence, and an HLA heavy chain sequence. In embodiments, the HLA heavy chain binding peptide and the HLA heavy chain sequence are covalently attached by a disulfide bond.

The present invention relates to mimics of post-translationally modified naturally occurring peptides, wherein said peptide mimics bind to a peptide-binding groove of human leukocyte antigen (HLA) molecules to the same extent as the naturally occurring post-translationally modified peptide, wherein said peptide mimics are recognized by T cells to the same extent as the naturally occurring post-translationally modified peptide, and additionally wherein said peptide mimics have a three-dimensional structure substantially identical to said post-translationally modified naturally occurring peptide. Such peptide mimics can be used alone of bound to a carrier, and have utility inter alia in methods for the treatment, alleviation and prevention of autoimmune diseases, and as components in tolerogenic vaccines.

Embodiments of the present disclosure pertain generally to head and neck squamous cell carcinomas (HNSCCs) related to human papillomavirus subtype 16 (HPV16) infections. More particularly, the present disclosure provides novel immunogenic epitopes from HPV16 E2, E6 and E7 antigens restricted by common human leukocyte antigen (HLA) alleles for the diagnosis and treatment of HNSCC. The HPV16 epitopes identified in the present disclosure can be used in combination with blockade of HPV16+ HNSCC-specific checkpoints for targeted immunotherapy.

The present application relates to the field of medical detection, and in particular, the present application relates to a kind of integrated genotyping method of multiple blood cell antigens related to selective blood transfusion and application thereof.The genotyping method described in the present application is an integrated typing method based on DNA sequence related to multiple red blood cell, platelet and white blood cell antigen coding genes related to blood transfusion, which can reduce the incidence of xenoantigen sensitization caused by alloimmunization, promote precision blood transfusion, and cover blood group genes including ABO, RhD, RhCE, HPA (ITGB3, GP1BA, GP1BB, ITGA2B, ITGA2, CD109, GP9), HLA-A, -B, -C, -DRB1, -DQB1, ABO, FUT1, FUT2, etc.The covered alleles can reach tens of thousands.Moreover, after the platform built in the present application, second-generation sequencing library construction and third-generation sequencing library construction can be carried out, which provides an excellent re-creation and reproduction platform for future haplotype confirmation of multiple site variations in blood group genes, and has important significance for future precision blood transfusion.

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).

A tumor neoantigen prediction method and a tumor neoantigen prediction system are provided. In the method, multiple amino acid sequences in genes of a person to be tested are extracted as multiple test peptides to be compared with multiple human protein sequences in a protein sequence database to find multiple similar peptides that match the human protein sequences. The similar peptides are filtered out from the test peptides and the filtered test peptides are input to multiple trained human leukocyte antigen (HLA) models to obtain multiple ranking results of the test peptides. A weighted sum of rankings of each test peptide in the ranking results is calculated as a score of the test peptide. At least one of the test peptides is selected as a neoantigen adapted for the person to be tested according to the score.

This document provides genetically modified cells compatible with multiple subjects, such as universal donor cells; and methods for generating said genetically modified cells. These universal donor cells contain at least one genetic modification within or near at least one gene encoding a survival factor, wherein the genetic modification includes the insertion of a polynucleotide encoding a tolerogenic factor. These universal donor cells may further contain at least one genetic modification within or near a gene encoding one or more MHC-I or MHC-II human leukocyte antigens or components or transcriptional regulatory factors of the MHC-I or MHC-II complex, wherein said genetic modification includes the insertion of a polynucleotide encoding a second tolerogenic factor.

Provided are TCR mimetic T cell engaging antibodies or antigen binding portions thereof that specifically bind antigens relating to hematological or myeloid malignancies, various compositions of such antibodies or antigen binding portions thereof, and methods of their use. The disclosure provides such antibodies, fragments of such antibodies retaining hematological or myeloid malignancy antigen-binding ability, pharmaceutical compositions including such antibodies or antigen binding fragments thereof, and diagnostic compositions including such antibodies or antigen binding fragments thereof. This disclosure further provides for isolated nucleic acids encoding such antibodies amino acid sequences of such antibodies, and host cells transformed therewith. Additionally, this disclosure provides for therapeutic and diagnostic methods employing the antibodies and nucleic acids of the disclosure. Finally, the present disclosure provides for recombinant trispecific antibodies capable of specifically binding CGI, CD3, and CD28.

The present invention discloses a hybridoma cell with a microbial preservation number of CCTCC NO: C2024193. The antibody secreted by the hybridoma cell can efficiently recognize the α3 domain of porcine major histocompatibility complex class I antigen in vivo or in vitro, and has prospects for medical applications.

The invention provides therapeutic cells that are comprehensively immune protected having a reduced or eliminated surface leukocyte antigen class I, an enhanced SIRPa engager (SIRPaE) expression, and an enhanced Fc sequestration molecule expression. In some aspects, the cells of the invention engage one or both of CD200R or CD99 ligands on immune cells. In other aspects, the cells of the invention sequester antibodies to inhibit humoral immunity. In other aspects, the cells of the invention have reduced or eliminated leukocyte antigens from both class I and class II. In other embodiments, the cells of the invention are ABO or Rh compatible with a recipient subject. In other embodiments, the cells of the invention are allogeneic or xenogeneic to the recipient.