96 results about "Cellular receptor" patented technology

The presently disclosed subject matter provides for methods and compositions for treating cancer (e.g., breast cancer). It relates to mutant PIK3CA-targeted TCRs that specifically target a mutant PIK3CA peptide (e.g., a human mutant PIK3CA peptide), and immunoresponsive cells comprising such TCRs. The presently disclosed mutant PIK3CA peptide-specific TCRs have enhanced immune-activating properties, including anti-tumor activity.

The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and / or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

This invention provides an antibody composition with improved stability, exhibiting reduced fragmentation of the antibody polypeptide chain during manufacturing and subsequent storage. [Solution] This disclosure relates to improved compositions and methods for treating T cell-mediated diseases and disorders (e.g., autoimmune disorders, graft-versus-host diseases, and graft rejection). Provided are antibody-containing anti-αβTCR binding polypeptides comprising at least one amino acid substitution or modification that enhances the stability of the binding polypeptide by reducing fragmentation of the light chain variable region. Methods provided herein generally involve administering an effective amount of a stabilized, humanized binding polypeptide specific to the alpha-beta T cell receptor (αβTCR) to a subject in need thereof.

The present invention provides a T-cell receptor (TCR) that binds to an immunogenic peptide when the peptide is presented by the major histocompatibility complex (MHC).

This document provides methods and materials for assessing and / or treating subjects (e.g., humans) suspected of having cancer. For example, this document provides methods and materials for a nucleic acid sequence analysis which can determine a sequence of B cell receptor. In some cases, determining a sequence of B cell receptor (and, optionally, identifying the presence of one or more mutations and / or identifying the presence of aneuploidy) in DNA (e.g., cell-free DNA (cfDNA)) in a fluid sample (e.g., a cerebrospinal fluid sample) obtained from a subject (e.g., a human subject such as a human suspected of having cancer) can be used to identify the subject as having cancer.

The present invention provides a T cell receptor (TCR) capable of specifically binding a short peptide KASEKIFYV (SEQ ID NO:9) derived from an SSX2 antigen. The antigen short peptide KASEKIFYV (SEQ ID NO:9) can form a complex with HLA A0201 and be presented together to a cell surface. The present invention further provides a nucleic acid molecule encoding the TCR and a vector comprising the nucleic acid molecule. In addition, the invention further provides a cell that transduces the TCR of the present invention.

The invention is directed to methods for determining antigen-specific T cells generally and to T cell receptors which bind an epitope of the Wilms' tumor antigen-1 (WT1) protein specifically. The disclosure also provides polynucleotides encoding the TCRs, engineered cells exogenously expressing the TCRs, and methods of making and using the TCRs and / or cells expressing the TCRs.

The present invention inter alia relates to a T-cell expressing a chimeric CD 95 receptor comprising a polypeptide, wherein said polypeptide comprises at least one CD 95-derived polypeptide region having at least 60% sequence identity with a polypeptide domain, a polypeptide region or a polypeptide motif of a human CD 95 wildtype receptor, wherein said human CD 95 polypeptide region comprises a CD 95 extracellular ligand binding domain; further wherein said polypeptide comprises at least one non-CD 95-derived co- stimulatory cytoplasmic polypeptide domain, region or motif of a tumor necrosis factor receptor superfamily protein comprising CD40, CD40L, CD27, HVEM, GITR, CD30, OX40, and / or LTBR, an immunoglobulin superfamily (IgSF) protein, a Toll-like-receptor, and / or an IL6-receptor family protein; wherein the T-cell further expresses an engineered T-cell receptor. The present invention also relates to a vector comprising nucleic acids encoding for the CD 95 receptor and the engineered T-cell receptor, as well as to a kit for preparing the T-cells of the present invention, and a pharmaceutical composition comprising the T-cells. The invention also relates to a method for preparing a T-cell for immunotherapy, and to a method for treating a patient having a disease comprising administering the pharmaceutical composition.

This invention belongs to the field of biomedical technology, specifically disclosing the application of a CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid in the preparation of a drug for treating tumors. Through analysis of the COSMIC database, epitope prediction, and in vitro and in vivo immunomodulatory activity experiments, this invention identified an HLA-A2-restricted CTL epitope peptide derived from the neoantigen ESR1. This mutant epitope peptide originates from a high-frequency mutation of ESR1 and can effectively stimulate and induce the production of neotope-specific cytotoxic T lymphocytes, specifically distinguishing between wild-type and mutant sequences, and killing tumor cells expressing the mutant epitope, exhibiting good anti-tumor effects. The resulting drug for treating tumors may contain the CTL epitope peptide derived from the neoantigen ESR1 or its encoded nucleic acid, or may contain a T-cell receptor, chimeric antigen receptor, or its encoded nucleic acid that specifically recognizes the mutant epitope peptide, demonstrating good therapeutic potential and clinical application prospects.

Multimodal cancer immunotherapy is a combination of cancer immunotherapies used to treat cancer in patients. T cell receptor diversity is used as a component of a method to treat cancer involving cancer therapy, including multimodal cancer immunotherapy.

The present disclosure provides orthogonal chimeric cytokine receptor / orthogonal cytokine pairs and compositions and methods for modified immune cells or precursors thereof (e.g., modified T cells) comprising an orthogonal chimeric cytokine receptor (e.g., an oIL2R-IL9R chimeric receptor) and a chimeric antigen receptor (CAR) or a T cell receptor (TCR). The present disclosure further provides an oncolytic adenoviral vector comprising a nucleic acid sequence encoding an orthogonal cytokine (e.g., oIL2), as well as methods of using the modified cells and the vector for treating cancer in a subject in need thereof.

An agent including a glycan-specific IgG antibody moiety, a cellular receptor binding moiety which binds to hepatocytes or other degrading cells through asialoglycoprotein (ASGPR) receptors of hepatocytes or other cell receptors which are on the surface degrading cells in a patient or subject, and optionally, a linker moiety connecting the glycan-specific IgG antibody moiety and the cellular receptor binding moiety.

MULTISPECIFIC MOLECULES BINDING TO TCR AND USES THEREOF ABSTRACT Provides herein are multifunctional molecules comprising T cell receptor variable beta-binding moieties, and methods of treating conditions or diseases in a subject using the same.

The invention provides a T cell wherein one or more therapeutic transgenes is integrated at a within the genome of the cell such that expression of the transgene is under control of an endogenous promoter of the T cell. The invention additional provides methods of making and using such cells to treat a subject with T cell therapy. The invention also provides a T cell wherein a recombinant nucleic acid sequence encoding a chimeric antigen receptor (CAR) is integrated at a first site within the genome of the cell such that the CAR is expressed by the cell at the surface of the cell, and wherein integration of the nucleic acid encoding the CAR at the first site reduces or prevents expression of a functional T cell receptor (TCR) complex at the surface of the cell. The invention additional provides methods of making and using such cells to treat a subject with CAR therapy.

An isolated or purified T cell receptor (TCR) is disclosed that has antigen specificity for a mutant human RAS amino acid sequence in which glycine at position 12 is substituted with valine. The TCR can recognize G12V RAS presented by HLA-DR heterodimers. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods for detecting the presence of cancer in a mammal and methods for treating or preventing cancer in a mammal.

Systems and methods include techniques associated with one or more machine learning systems to predict a likelihood of binding between a target peptide and a T-cel receptor. The one or more machine learning systems may be used to generate a binding score for one or more binding amino acids of the target peptide including one or more physical or chemical properties of the binding interaction.

Provided herein are engineered T-celi receptors (TCRs) having nanomoiar affinity for the immuno-dominant pp65 peptide residing between residues 495-503 (NLV) in complex with HLA-A2*02:01. The TCRs may be membrane-hound TCRs, soluble TCRs, chimeric TCRs, or chimeric antigen receptors. Also provided are methods of using the engineered TCRs to treat diseases, monitor disease progression, monitor vaccine efficacy, and detecting NLV / A2 presentation on the surface of cells.

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

The present disclosure provides an oligonucleotide conjugate, which is obtained by covalently linking a kidney-targeting polypeptide as a ligand to an oligonucleotide molecule capable of inhibiting the expression of a target gene via a linker group. The oligonucleotide conjugate has affinity to a cell receptor present on a kidney target cell, and can selectively and effectively reduce or inhibit the expression of a target gene in the kidney of a subject (e.g., a human or an animal). The oligonucleotide conjugate or pharmaceutical composition provided by the present disclosure can effectively treat and / or prevent a pathological condition or disease caused by abnormal expression of a specific gene in kidney tissue cells.

This invention relates to the use of "off-the-shelf" allogeneic therapeutic cells in combination with chemotherapy for the treatment of cancer patients. In particular, the inventors have developed a method for engineering allogeneic T-cells resistant to chemotherapy agents. The therapeutic benefits provided by this strategy should be enhanced through the synergistic effect between chemotherapy and immunotherapy. Specifically, this invention relates to a method for modifying T-cells by inactivating at least one gene encoding a T-cell receptor component and by modifying said T-cells to confer drug resistance. This invention opens the door to standard and affordable adoptive immunotherapy strategies for treating cancer.

This disclosure relates to a method for determining the potency of an effector cell composition, such as a therapeutic cell composition, for use in conjunction with cell therapy, based on cytotoxicity. The cells of the cell composition may express recombinant receptors, such as chimeric receptors, such as chimeric antigen receptors (CARs), or other transgenic receptors such as T cell receptors (TCRs). The method provides a cytotoxicity assay for identifying the potency of the cell composition, including relative potency.

Provides herein is method of treating a disease or condition in a subject, or a combination therapy using agents that bind to a T cell receptor alpha variable region (TCRαV) and / or a T cell receptor beta variable region (TCRβV).

Compositions and methods for specific expression of RNA or protein are provided, such as a Chimeric Antigen Receptor (CAR) or T Cell Receptor (TCR), in T cells, with limited or no expression in non-T cells.

Provided herein are T cell receptors (TCRs) or antigen-binding fragments thereof, such as those that recognize or bind NPM1c neoantigens. In particular, the present disclosure relates to TCRs that bind or recognize specific NPM1c peptides in the context of major histocompatibility complex (MHC) molecules. The present disclosure also relates to nucleic acids encoding such TCRs, engineered cells comprising such TCRs, methods of isolating such TCRs, and uses thereof, e.g., in cell therapy.

The antibodies of the present invention have specific binding activity to HLA-DQ2.5 and may have binding activity to HLA-DQ2.2 and / or HLA-DQ7.5, but substantially no binding activity to HLA-DQ8, HLA-DQ5.1, HLA-DQ6.3, HLA-DQ7.3, HLA-DR, HLA-DP, or a complex of the invariant chain (CD74) and HLA-DQ2.5. The antibodies bind to HLA-DQ2.5 in the presence of a gluten peptide such as gliadin, i.e., bind to HLA-DQ2.5 forming a complex with the gluten peptide. The antibodies have neutralizing activity against the binding between HLA-DQ2.5 and TCR, and thus block the interaction between HLA-DQ2.5 and an HLA-DQ2.5-restricted CD4+ T cell. The antibodies do not undergo rapid internalization mediated by the invariant chain.

The present invention relates to an engineered regulatory T cell (Treg) comprising a T cell receptor (TCR) which is capable of specifically binding to a myelin basic protein (MBP) peptide or variant or fragment thereof when the peptide is presented by a major histocompatibility complex (MHC) molecule. The present invention further relates to methods for providing an engineered Treg and to methods and uses of said engineered Treg and vectors and kits of vectors encoding said Treg.

Provided in the present invention is a T cell receptor engineering modification method, which comprises the steps of: obtaining CDR regions of a given T cell receptor sequence by means of a database, mutating one or more amino acid residues in the CDR regions into histidine, and establishing a first T cell receptor mutation library. The T cell receptor engineering modification method provided by the present invention is based on a histidine scanning method, realizes TCR engineering modification independent of three-dimensional structures, overcomes the disadvantages of high affinity and realizes the modification of TCRs with low affinity and high activation, thereby providing more options for clinical use. The T cell receptor provided by the present invention comprises the following six CDR regions, CDR1α, CDR2α and CDR3α in a TCRα chain, and CDR1β, CDR2β and CDR3β in a TCRβ chain, the amino acid sequences of which are shown as SEQ ID No. 1-6, respectively. In the present invention, engineering modification of a wild-type MAGE-A3 TCR molecule is achieved by means of a catch bond to obtain an efficient and non-toxic TCR targeting MAGE-A3, which is free of toxic and side effects caused by affinity maturation. Moreover, the engineered TCR is applied to TCR-T cell preparation for solid tumor treatment.

To provide a further method for treating cancer.SOLUTION: Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for a mutated human RAS amino acid sequence with a substitution of glycine at position 12 with arginine. Related polypeptides and proteins, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions are also provided. Also disclosed are methods of detecting the presence of cancer in a mammal and methods of treating or preventing cancer in a mammal.SELECTED DRAWING: Figure 1