39 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 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 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.

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.

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.

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).

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 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 invention relates to the field of biomedical testing technology, and in particular to a primer set, kit, and genotyping method for accurately achieving ultra-high resolution genotyping of 11 human leukocyte antigen (HLA) loci based on nanopore sequencing technology. The present invention provides a primer set for ultra-high resolution HLA genotyping, which is used for multiplex amplification of HLA genes and includes primer pairs for HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3 / 4 / 5, HLA-DQA1, HLA-DQB1, HLA-DPA1, and HLA-DPB1 loci. The primer set of the present invention for multiplex amplification of 11 genes for HLA typing can achieve simultaneous amplification of each gene at the HLA gene HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DRB3, HLA-DRB4, HLA-DRB5, HLA-DQA1, HLA-DQB1, HLA-DPA1 and HLA-DPB1 loci in a single reaction system, thereby improving the integrity, efficiency and uniformity of gene amplification and the accuracy of subsequent HLA genotyping.

Provided herein are genetically modified cells, such as universal donor cells, compatible with multiple subjects; and methods of producing the genetically modified cells. The invention relates to universal donor cells comprising at least one genetic modification within or near at least one gene of a component or transcriptional regulatory factor encoding one or more MHC-I or MHC-II human leukocyte antigens or MHC-I or MHC-II complexes, at least one genetic modification that increases expression of at least one polynucleotide encoding a tolerogenic factor, and optionally at least one genetic modification to increase or decrease the expression of at least one gene encoding a survival factor.

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.

Provided are compositions and methods for prophylaxis and / or therapy of a variety of cancers which express a NY-ESO-1 antigen. Included are recombinant T cell receptors (TCRs), polynucleotides encoding them, expression vectors that include the polynucleotides, and cells into which the polynucleotides have been introduced to produce modified cells, including CD4+ T cells, CD8+ T cells, natural killer T cells, γδ T cells, and progenitor cells, such as haematopoietic stem cells. The modified cells are capable of direct recognition of a cancer cell expressing a NY-ESO-1 antigen by human leukocyte antigen (HLA) class II-restricted binding of the TCR to the NY-ESO-1 antigen expressed by the cancer cell without presentation of the antigen by antigen presenting cells. In embodiments, the NY-ESO-1 antigen is displayed by the tumor cells. Also included is a method for prophylaxis and / or therapy of cancer by administering modified cells that express a recombinant TCR. Methods for making expression vectors and / or cells which express a recombinant TCR and identifying TCRs to make the expression vectors are also included.

The disclosure relates to antibody products specific for human leukocyte antigens and related methods. The products can be used in diagnosis and methods of treatment of disease, such as in methods of diagnosing and treating Graft Versus Host Disease (GVHD).

The present invention relates to a biological sample bank comprising at least two cell biological sample banks wherein the cells of the cell biological sample bank may be immune cells or hematopoietic stem and progenitor cells (HSPC) or in vitro produced T cell progenitor cells wherein the cells of each cell bank have a specific homozygous human leukocyte antigen (HLA) haplotype. The invention also relates to a method for selecting at least one cell bank, and to the use of the selected cell bank as an agent, in particular for the treatment of immunodeficiencies, immune disorders and / or diseases, lymphopenia or cancer, and covering a large number of patients.

The present disclosure relates to an engineered T-cell Receptors (TCRs) capable of binding to an epitope of an epidermal growth factor receptor (EGFR) comprising a T790M mutation presented on human leukocyte antigen-A (HLA-A)*02:01, wherein the epitope comprises the amino acid sequence of MQLMPFGCLL (SEQ ID NO: 1). Also disclosed are Tcell and BiTE therapies comprising the same, and methods of treating EGFR-TKI resistant lung cancers using the same.

Genetically modified cells that are compatible with multiple subjects, e.g., universal donor cells, and methods of generating said genetic modified cells are provided herein. The universal donor cells comprise at least one genetic modification within or near at least one gene that encodes one or more MHC-I or MHC-II human leukocyte antigens or component or transcriptional regulator of the MHC-I or MHC-II complex, at least one genetic modification that increases the expression of at least one polynucleotide that encodes a tolerogenic factor, and optionally at least one genetic modification that increases or decreases the expression of at least one gene that encodes a survival factor.

Provided is an engineered cell expressing truly epitope-receptive MHC ectodomains, comprising a human leukocyte antigen molecule (HLA molecule), wherein the HLA molecule comprises a first chain and a second chain, wherein the first chain of the HLA molecule is selected from HLA-I heavy chains or HLA-II alpha chains, the second chain of the HLA molecule is selected from HLA-I light chains or HLA-II beta chains, and the first and second chains of the HLA molecule are non-covalently linked to form an HLA molecule with native HLA molecular functions. The engineered cells can be used for rapid identification and characterization of MHC restricted antigen peptides, and can efficiently and accurately develop and validate HLA neoantigen targeting immunotherapeutic biologics and drug candidates.