41 results about "Major histocompatibility" patented technology

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors as well as genetically edited or otherwise engineered enhance the persistence the cells in immunotherapy. In several embodiments, the cells are edited to knock out a target gene that encodes a protein involved in antigen processing and presentation by major histocompatibility complex class I molecules. In several embodiments, a mixture of immune cell types is used, optionally in allogeneic therapy. The engineering and editing of the cells, such as NK cells and / or T cells exhibit enhanced cytotoxicity and / or persistence, as well as reduced risk of reduced graft versus host, host versus graft, and graft versus graft effects.

Surrogate co-receptors for T cells, including T cells expressing chimeric receptors comprising major histocompatibility molecules grafted onto T cell receptor molecules. The surrogate co-receptors feature a portion of CD8, wherein the Ig domains of CD8 are replaced with Ig domains that confer novel specificities (e.g. antibody Fv fragments specific for a target of interest.) The surrogate co-receptors may be used to help enhance CRMpMHC-CD3 signaling as part of a 5-module receptor system. The present invention also describes Lck fusions.

This document provides methods and materials involved in treating myeloid neoplasms (e.g., myeloid cancers such as acute myeloid leukemia (AML)). For example, methods and materials for making and / or using T cells expressing (e.g., engineered to express) (a) one or more chimeric antigen receptors (CARs) having the ability to bind to a myeloid-specific polypeptide (e.g., a CD33 polypeptide) and (b) one or more inhibitory CARs (iCARs) having the ability to bind to a class I major histocompatibility complex (MHC) polypeptide (e.g., an HLA-A polypeptide such as an HLA-A2 polypeptide). In some cases, T cells provided herein can be administered to a mammal (e.g., a human) having a myeloid neoplasm (e.g., a myeloid cancer such as AML) and having received a haploidentical bone marrow transplant to target (e.g., target and destroy) the mammal's myeloid cells while sparing the donor-derived myeloid cells.

The invention provides genetically modified non-human animals that express chimeric human / non-human MHC I polypeptide and / or human or humanized β2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a humanized T cell co-receptor (e.g., humanized CD4 and / or CD8 (e.g., CD8α and / or CD8β)), a human or humanized T cell receptor (TCR) comprising a variable domain encoded by at least one human TCR variable region gene segment and / or a human or humanized major histocompatibility complex that binds the humanized T cell co-receptor (e.g., human or humanized MHC II (e.g., MHC II α and / or MHC II β chains) and / or MHC I (e.g., MHC Iα) respectively, and optionally human or humanized β2 microglobulin). Also provided are embryos, tissues, and cells expressing the same. Methods for making a genetically engineered animal that expresses at least one humanized T cell co-receptor (e.g., humanized CD4 and / or CD8), at least one humanized MHC that associates with the humanized T cell co-receptor (e.g., humanized MHC II and / or MHC I, respectively) and / or the humanized TCR are also provided. Methods for using the genetically engineered animals that mount a substantially humanized T cell immune response for developing human therapeutics are also provided.

The application discloses a preparation method and application of a hollow manganese dioxide nanocarrier coated with a human umbilical cord mesenchymal stem cell membrane and a transmembrane peptide TAT, and is characterized in that: hollow mesoporous manganese dioxide is synthesized through a selective etching technology, and a layer of human umbilical cord mesenchymal stem cell membrane is coated outside the manganese dioxide through a repeated extrusion method. Since the cell membrane has special tumor homing characteristics, and lacks major histocompatibility complex-II and only expresses major histocompatibility complex-I in a trace amount, the key scientific problems and difficulties such as low biological safety, strong immunogenicity and easy elimination by the body of artificially synthesized nanomaterials can be effectively solved. Finally, the cell membrane surface is modified with the transmembrane peptide TAT through a phospholipid insertion method, precise subcellular localization-nucleus targeting is realized, and tumor cells can be more effectively killed.

Radionuclide-labeled soluble biologics directed against peptide presenting Major Histocompatibility Complexes (pMHCs), and methods for treating cancers using the biologics are provided. Soluble biologics include recombinant T-cell receptor proteins (rTCR) and TCR-antibody mimics that specifically bind to pMHCs. The soluble biologics may further include a heavy chain of IgG1, IgG2, IgG4, or variants thereof. The radioisotopes used to label the soluble biologic may include alpha-emitting isotopes, such as actinium-225, or beta-emitting isotopes, such as lutetium-177, and may be administered at a maximum tolerated dose in a single bolus or in fractionated doses that together equal the maximum tolerated dose. The methods may further include administration of additional therapeutic agents or modalities.

The present disclosure is directed to antigen-binding molecules that specifically bind peptide fragments of tumor antigens, wherein the peptide fragment is capable of being presented by more than one type of major histocompatibility complex (MHC) class II molecule. In some aspects, the tumor antigen is a WT1 polypeptide. Other aspects are directed to antibodies, multispecific antibodies, and chimeric antigen receptors, and nucleotides encoding the same. Other aspects are directed to methods of administering the same to a subject in need thereof.

Single-domain antibodies that specifically bind human papillomavirus (HPV) E6 or E7 oncogenic peptides in complex with human major histocompatibility complex (MHC) proteins are described. The E6-MHC-specific and E7-MHC-specific single-domain antibodies were isolated from dromedary camel (VHH) antibody libraries by panning the library with an E6- or E7-derived peptide in complex with HLA-A*02:01. Use of the single-domain antibodies for the detection and treatment of HPV-associated cancers and pre-cancerous lesions is also described.

The present invention provides a T cell receptor (TCR) that binds to immunogenic peptides when presented by major histocompatibility complexes (MHCs).

The present disclosure relates to a novel vaccine strategy against hepatitis B virus (HBV) infection, which is a major cause of chronic liver disease and hepatocellular carcinoma worldwide. The disclosure provides fusion proteins that target dendritic cells (DCs), the key antigen-presenting cells of the immune system, and deliver HBV-derived peptides to both the major histocompatibility complex (MHC) class I and II pathways, thereby inducing strong and specific humoral and cellular immune responses against the viral envelope and core antigens. The disclosure also provides methods of using the fusion proteins for the prevention or treatment of HBV infection and its complications. The inventors have demonstrated in a mouse model that the DC-targeting HBV vaccine candidates can elicit robust antibody and T cell responses, which are essential for the clearance of the virus and the protection from chronic infection.

The present invention relates to a bispecific polypeptide molecule comprising a first polypeptide chain and a second polypeptide chain providing a binding region derived from a T cell receptor (TCR) being specific for a major histocompatibility complex (MHC)-associated peptide epitope, and a binding region derived from an antibody capable of recruiting human immune effector cells by specifically binding to a surface antigen of said cells, as well as methods of making the bispecific polypeptide molecule, and uses thereof.

The present invention relates to: a composition for delivering a viral antigen-derived CD8+ T cell antigen epitope or a peptide comprising same to the cytoplasm of a target cell to thereby present the epitope or peptide to major histocompatibility complex class I (MAC-1), which is an antigen-presenting molecule on the cell surface; a composition comprising same; and a use thereof.

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.

Artificial antigen presenting cells (aAPC) including a major histocompatibility class II (MHC II) molecule and methods of their use for identifying, isolating, or detecting one or more antigen-specific T cells, and treating a disease, disorder, or condition, including cancer, are disclosed.

Some embodiments of the methods and compositions provided herein relate to obtaining long read information from short reads of a target nucleic acid. Some embodiments include steps to selectively generate, mark, and amplify long nucleic acid fragments. Some embodiments include enriching for certain sequences in the long fragments with selection probes directed to major histocompatibility complex (MHC) genes. Some embodiments also include fragmenting the long nucleic acid fragments into shorter fragments for sequencing, and informatically reconstructing a sequence of the target nucleic acid.

The present invention generally relates to the production and use of antigen-binding proteins. The invention relates to heteromeric antigen-binding proteins, their production and their use. In particular the invention relates to the combination of an antigen-binding protein binding to a peptide according to SEQ ID NO: 57 or to the peptide according to SEQ ID NO: 57 bound to a major histocompatibility complex (MHC) protein and an antigen-binding protein binding to a peptide according SEQ ID NO: 58 or to the peptide according to SEQ ID NO: 58 bound to a major histocompatibility complex (MHC) protein and optionally one or more further antigen-binding proteins. Furthermore, the invention relates to heteromeric antigen-binding proteins with improved heterodimerisation properties and correspondingly improved production properties. The invention also relates to co-expression of at least two heteromeric antigen-binding proteins. The invention further relates to heteromeric antigen-binding proteins for use in the treatment of diseases, in particular cancer, optionally wherein nucleic acids encoding said antigen-binding proteins are administered to the subject.

The present disclosure provides a method for purifying a T cell-engaging peptide-major histocompatibility complex binding domain (TCE-pMHC) molecule produced by a host cell, the method comprising: separating a supernatant of a host cell culture comprising the TCE-pMHC molecule to form a product (a); subjecting product (a) to affinity chromatography to form product (b) wherein the TCE-pMHC molecule is eluted by the affinity chromatography at a pH of from about 3.0 to about 4.0; neutralizing product (b) by adding an MES buffer having a pH of less than 7.0 to form product (c) wherein the pH of product (c) is from about 5.0 to about 7.0; and subjecting the product (c) to anion exchange chromatography to form a product (d); wherein the pMHC binding domain and the T cell-engaging immune effector domain are capable of binding to a pMHC complex and a T cell, respectively.

The present invention relates to the field of biotechnology, specifically to bivalent bispecific chimeric antibodies that include a heterodimer based on the membrane-proximal domains of MHC (major histocompatibility complex) or MHC-like proteins (CD1 (cluster of differentiation 1) or HFE (hemochromatosis protein)), as well as to a technique for producing said bispecific antibodies. The invention further relates to a nucleic acid encoding said bispecific antibody, an expression vector, a host cell for producing said bivalent chimeric bispecific antibody and to a method for producing said cell.

The present invention relates to the field of cancer immunotherapy. In particular, the present application relates, in some aspects, to binding molecules, such as complexes capable of specifically binding a major histocompatibility complex (MHC) molecule and an AFP peptide. The present invention relates to T cell receptors (TCRs), including antigen binding domains thereof, that bind to or recognize such peptide epitopes. The present application further relates to engineered cells comprising such binding molecules, such as TCR double antibody proteins or TCRs, and the like, and their use in cancer immunotherapy.

The present disclosure relates to the identification of single nucleotide polymorphisms (SNPs) in the Gamma genomic block in the central region of the major histocompatibility complex (MHC) that can be used for matching transplant donors and recipients and determining disease susceptibility.

Artificial antigen presenting cells (aAPC) including a major histocompatibility class II (MHC II) molecule and methods of their use for identifying, isolating, or detecting one or more antigen-specific T cells, and treating a disease, disorder, or condition, including cancer, are disclosed.

Immunogenic compositions comprising one or more peptides, wherein the one or more peptides: are capable of binding to Major Histocompatibility Complex (MHC) class II, and are derived from one or more translation products of SARS-CoV-2. Also provided include methods of treating and preventing diseases using the immunogenic compositions.

The invention discloses a tumor shared cell membrane antigen epitope peptide and a screening method thereof. The method comprises the following steps: (1) screening an induced pluripotent stem cell membrane and a human tumor cell membrane to obtain protein with high expression difference compared with a normal body cell membrane; (2) screening amino acid sequences which are strongly combined with a human or mouse major histocompatibility compound from the amino acid sequences of the differentially highly expressed proteins to obtain candidate epitope peptides; (3) screening the candidate epitope peptide with high population coverage rate according to the proportion of each subtype human main histocompatibility compound strongly bound with the candidate epitope peptide in the population; and (4) detecting candidate epitope peptides with a high population coverage rate by using a nano vaccine platform, wherein the epitope peptide capable of triggering a specific immune reaction is the tumor shared cell membrane antigen epitope peptide. According to the method, the tumor shared cell membrane antigen epitope peptide can be successfully screened, and the screened tumor shared cell membrane antigen epitope peptide has an obvious anti-tumor effect in vivo.

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.

Provided herein are recombinant viral particles presenting on their surface a peptide presented in the context of a major histocompatibility complex (MHC) molecule for recognition by a T cell. The recombinant viral particles may further present on their surface a co-stimulatory domain. Also provided are methods of using the recombinant viral particles, for example, for activating T cells and for the treatment of disease.

Provided is a new composition capable of inducing an immune response against a target antigen. A composition according to the present disclosure comprises: a target antigen or a polynucleotide encoding the same; and an expression inducer of major histocompatibility gene complex class II (MHC class II molecule) and / or an expression inhibitor of an invariant chain thereof.

Soluble, multi-polypeptide multispecific protein for recruiting an immune cell to a target cell presenting a target peptide major histocompatibility complex (pMHC), for therapeutic use against diseases such as cancer Protein comprising (i) a pMHC binding arm comprising a dimer of a first portion and a second portion, (ii) an immune cell engager moiety, and (iii) an Fc region comprising a dimer of a first Fc portion and a second Fc portion, wherein the first portion of the pMHC binding arm is linked at its N terminus to the immune cell engager moiety, and wherein the second portion of the pMHC binding arm is linked at its N terminus to a C terminus of the first Fc portion, and an N terminus of the Fc region is linked to a C terminus of the pMHC binding arm.

This invention relates engineered extracellular vesicles (EVs) comprising a membrane-bound interleukin-2 (IL-2) molecule and / or functional fragment thereof, a major histocompatibility (MHC) molecule and / or functional fragment thereof, and one or more costimulatory molecule, each expressed on the surface membrane of the EV. The invention further relates to compositions, cells and kits comprising the same, and methods of using and making the same.