51 results about "T-Cell Receptor Gene" patented technology

The present invention provides antigen binding proteins that specifically bind to Wilms' tumor protein (WT1), including humanized, chimeric and fully human antibodies against WT1, antibody fragments, chimeric antigen receptors (CARs), fusion proteins, and conjugates thereof. The antigen binding proteins and antibodies bind to HLA-A0201-restricted WT1 peptide. Such antibodies, fragments, fusion proteins and conjugates thereof are useful for the treatment of WT1 associated cancers, including for example, breast cancer, ovarian cancer, prostate cancer, chronic myelocytic leukemia, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myeloid / myelogenous leukemia (AML) and myelodysplastic syndrome (MDS). In more particular embodiments, the anti-WT1 / A antibodies may comprise one or more framework region amino acid substitutions designed to improve protein stability, antibody binding and / or expression levels.

A method of sequencing a population of polynucleotides encoding antibodies or T-cell receptors. Also provided are a method of quantifying an expression of a population of polynucleotides encoding antibodies or T-cell receptors as well as an oligonucleotide library for sequencing by hybridization of polynucleotides encoding variable regions of antibodies or T cell receptors.

The invention is directed to a method of monitoring or detecting treatment-resistant clones in a patient being treated for a lymphoid or myeloid neoplasm from which patient-specific correlating clonotypes have been identified. In some embodiments, such method includes the steps of obtaining a sample from the patient comprising T-cells and / or B-cells; amplifying molecules of nucleic acid from the T-cells and / or B-cells of the sample, the molecules of nucleic acid comprising recombined DNA sequences from T-cell receptor genes or immunoglobulin genes; sequencing the amplified molecules of nucleic acid to form a clonotype profile; determining from the clonotype profile a level of each correlating clonotype and clonotypes clonally evolved therefrom; and correlating a presence of a treatment-resistant clone of the neoplasm with a change in relative levels of the correlating clonotypes and clonotypes clonally evolved therefrom. In part, the invention permits one to distinguish between cases where treatment is effective but insufficiently intense and cases where a cancer clone arises that is resistant to a current treatment approach.

The invention relates to the field of cytogenetics and the application of genetic diagnostic techniques in pathology and hematology. Specifically, the invention relates to nucleic acid probes that can be used in hybridization techniques for the detection of chromosomal aberrations and other gene rearrangements such as immunoglobulin and T-cell receptor gene rearrangements. The probes provided by the invention are a distinct and balanced set of probes of comparable size, each preferably being from 1 to 100 kb, or smaller, and flanking a potential breakpoint in a chromosome.

The invention belongs to the technical fields of immunology and tumor therapy, and relates to a preparation method and a use of a TCR gene modified CD8+T memory stem cell. The method comprises the following steps: co-incubating a tumor antigen and an immature dendritic cell to obtain a specific tumor antigen-supported mature dendritic cell, co-culturing the specific tumor antigen-supported maturedendritic cell and a CD8+ naive T cell, and adding a stem cell differentiation inhibitor to promote the generation of a CD8+ stem cell-like memory T lymphocyte; separating the CD8+ stem cell-like memory T lymphocyte; and cloning a T cell receptor gene (TCR) for specifically identifying a specific antigenic epitope, and carrying out lentivirus packaging or retroviral vector cotransfection on an autologous CD8+ Tscm cell to in-vitro prepare a CD8+ TCR-Tscm cell specific for different tumor specific antigens. The CD8+ TCR-Tscm cell prepared by the method has the advantages of overcoming of the tumor heterogeneity, high specificity, few adverse reactions, and highly-efficient and lasting tumor preventing and treating effects.

The invention provides T-cell receptor (TCR) molecules comprising a Vα chain and a Vβ chain that bind peptides derived from the p53 protein, preferably, the human p53 protein. The TCR molecules include both heterodimeric molecules and single chain molecules which specifically bind a sequence preferably spanning about amino acid positions 264-272 of the p53 protein displayed in the context of an HLA molecule, preferably, HLA-A2.1. Also disclosed are methods for making and using such TCR molecules. The invention has a wide spectrum of useful application including therapeutic uses and use in the detection of cells expressing p53 protein.

Disclosed are: a nucleotide sequence and an amino acid sequence for CDR3 region of T-cell receptor (TCR) gene of WT1-specific cytotoxic T-cell (CTL) for WT1 protein; a method for the detection or treatment of cancer using the nucleotide sequence or the amino acid sequence; and a chip, a primer set, a kit, an apparatus and the like for use in the detection of cancer, each of which comprises the nucleotide sequence or the amino acid sequence.

The invention discloses a method for obtaining a tumor specific T cell receptor. The method comprises the following steps: firstly, obtaining a T cell receptor gene sequence in an antigen peptide specific T cell which comes from an immunoreactive positive and / or tumor symptom relieved tumor patient after antigen peptide treatment; then, preparing an antigen specific T cell receptor according to the antigen specific T cell receptor gene sequence; introducing the antigen peptide specific T cell receptor gene into the T cell, and expressing the antigen peptide specific T cell receptor gene to obtain the specific TCR-T cell. The specific TCR-T cell can be used for successfully killing gene mutation corresponding to antigen peptide and HLA typed tumor cell, and has high killing efficiency and agood application prospect.

Featured is T cell receptor complexes designed to redirect the immune system against various diseases. The T cell receptor complexes of the invention have been engineered to recognize target antigen in a functionally bispecific nature. Fusion protein complexes and protein conjugate complexes are comprised of high affinity antigen-specific TCR and biologically active proteins and / or effector molecules. Also featured is methods of production of T cell receptor fusion and conjugate complexes as well as therapeutic compositions for use of the complexes.

The invention provides a whole blood immune repertoire detection method based on high-flux sequencing technology. The method comprises the following steps: (1) directly extracting RNA (ribonucleic acid) from a whole blood sample; (2) carrying out reverse transcription on the RNA to generate single chain cDNA (complementary deoxyribonucleic acid), connecting an oligonucleotide joint sequence to the tail end of the single chain cDNA, carrying out PCR (polymerase chain reaction) reaction on the single chain cDNA subjected to oligonucleotide joint sequence connection by using a universal primer and a special targeted primer P-VDJ (of which the sequence is GAC CTC GGG TGG GAA CAC) as a special primer pair for PCR reaction, and amplifying the immune receptor genome; and (3) carrying out high-flux sequencing. The method of directly extracting the RNA from the whole blood sample is more suitable for clinic; the single target specific primer is utilized to uniformly amplify the variable region of the subtype T cell receptor gene; and a Hi-SEQ 2500 of the Illumina corporation and a bar code are utilized for sequencing, thereby ensuring the lower cost, the sequencing time of less than 48 hours and favorable sequencing depth.

The invention provides a T cell receptor (TCR) capable of specifically combining short-peptide PYLGQMINL derived from a PRAME antigen, and the antigenic short-peptide PYLGQMINL and HLA A2402 can form a compound and are together delivered to the cell surface. The invention further provides nucleic acid molecules encoding the TCR and a carrier comprising the nucleic acid molecules. The invention further provides a cell transducing the TCR.

Disclosed is an isolated or purified T cell receptor (TCR), wherein the TCR has antigenic specificity for mutated Kirsten rat sarcoma viral oncogene homolog (KRAS) presented by a human leukocyte antigen (HLA) Class II molecule. 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.

The invention provides a T cell receptor (TCR) which can be specifically combined with an NY-ESO-1 antigen short peptide SLLMWITQC. The antigen short peptide SLLMWITQC and HLA A0201 can form a composite which is presented onto the surface of the cells together. The invention also provides a nucleic acid molecule encoding the TCR and a carrier containing the nucleic acid molecule, and also provides a cell that transduces the TCR.

A non-human mammalian model of an autoimmune disorder co-expresses a major histocompatibility (MHC) class II-restricted T cell receptor (TCR) and a selected peptide that binds to the TCR. The selected peptide is selectively expressed by MHC class II positive antigen presenting cells (APC) of the mammal. Models with high penetrance of disease are those in which the selected peptide is a MHC class II-restricted T cell determinant that specifically binds with high affinity to the TCR. Models with low penetrance of disease are those in which the selected peptide binds with low affinity to the TCR. These models, which may be transgenic mammals, are used in method for identifying diagnostic and therapeutic markers and targets characteristic of an autoimmune disorder.

The present invention provides compositions comprising a protein expression blocker or PEBL comprising a target-binding molecule and localizing domain, and methods of using such compositions in cancer therapy. PEBLs are useful as a blockade of expression of target surface receptors (peptides or antigens) in immune cells. Also provided herein are CD3 / TCRαβ-deficient T cells and CD3 / TCRαβ-deficient chimeric antigen receptor T cells that express such PEBLs.

Compositions comprising a cell in which a molecular complex with high affinity for its cognate ligand is bound to the surface of the cell are provided. To form the molecular complexes, extracellular domains of transmembrane heterodimeric proteins, particularly T cell receptor and major histocompatibility complex proteins, can be covalently linked to the heavy and light chains of immunoglobulin molecules. The molecular complexes can be used, inter alia, to detect and regulate antigen-specific T cells and as therapeutic agents for treating disorders involving immune system regulation, such as allergies, autoimmune diseases, tumors, infections, and transplant rejection. Optionally, identical antigenic peptides can be bound to each ligand binding site of a molecular complex.

The present invention relates to T cell receptors (TCRs) which bind the HLA-A*0201 restricted peptide GVYDGEEHSV (SEQ ID NO: 1) derived from the MAGE-B2 protein. The TCRs of the invention demonstrateexcellent specificity profiles for this MAGE epitope. Also provided are nucleic acids encoding the TCRs, cells engineered to present the TCRs, cells harbouring expression vectors encoding the TCRs andpharmaceutical compositions comprising the TCRs, nucleic acids or cells of the invention.

Variable domain murine T-cell receptor genes have been isolated and used to construct cloning and expression vectors. Valpha, Vbeta, and single chain Valpha-Vbeta fragments have been expressed as secreted domains in Escherichia coli using the vectors. The domains are secreted into the culture supernatant in milligram quantities. The single domains and the single chain T-cell receptors are folded into beta-pleated sheet structures similar to those of immunoglobulin variable domains. The secreted fragments may be useful for immunization to generate anti-clonotypic antibodies, in vaccination or for high resolution structural studies. The genes encoding these domains may also serve as templates for in vitro mutagenesis and improvement of affinities of the TCR fragments for their interaction with cognate peptide-MHC complexes.

Provided is a method for inducing T cells for use in a cell-based immunotherapy, comprising the steps of:(1) providing human pluripotent stem cells bearing a T cell receptor specific for a WT1 antigen or an Epstein-Barr virus associated antigen, and(2) inducing T cell progenitors or mature T cells from the pluripotent stem cells provided in step (1). Pluripotent stem cells may preferably be iPS cells. The human pluripotent stem cells bearing a T cell receptor specific for an antigen may be prepared by inducing iPS cells from a T cell having the desired antigen specificity or by introducing genes encoding the T cell receptor specific for the desired antigen into iPS cells. The T cells obtained by this method can be used for the treatment of various immune-related diseases such as cancers and infectious diseases.

Provided is a method for immune cell therapy, which comprises generating T cell progenitors from pluripotent stem cells bearing rearranged T cell receptor genes and transferring the T cell progenitors to a patient in need of the treatment. The pluripotent stem cells may be iPS cells (T-iPS cells) bearing rearranged T cell receptor genes. By administering T cell progenitors instead of mature T cells, effective and safe immune cell therapy can be achieved.

The invention provides a T cell receptor (TCR) capable of specifically combining short-peptide PYLGQMINL derived from a PRAME antigen, and the antigenic short-peptide PYLGQMINL and HLA A2402 can form a compound and are together delivered to the cell surface. The invention further provides nucleic acid molecules encoding the TCR and a carrier comprising the nucleic acid molecules. The invention further provides a cell transducing the TCR.

The present invention provides a T cell receptor targeting MAGE-A3, the T cell receptor targeting MAGE-A3 comprises an alpha chain and a beta chain, the alpha chain comprises an amino acid sequence shown in SEQ ID NO: 1, and the beta chain comprises the amino acid sequence shown in SEQ ID NO: 2. The present invention also provides a T cell receptor gene-modified T cell targeting MAGE-A3. The T cell receptor gene-modified T cell targeting MAGE-A3 can efficiently and specifically kill MAGE-A3 positive cancer cells, has long-lasting vitality and lethality, and do not cause damage to normal cells.The invention also provides a preparation method of the T cell receptor gene-modified T cell targeting MAGE-A3 and an application thereof.

Disclosed are: polypeptides for TCR α-chain and β-chain which are restricted to HLA-A*0201 for Aur-A and are derived from a CTL; and nucleic acids encoding the polypeptides. The nucleic acids can impart a cytotoxic activity against a cell capable of presenting an HLA-A*0201 molecule and an Aur-A207-215 peptide thereon to a T cell, and are therefore useful for the treatment of cancer in which Aur-A is expressed.

The invention relates to the field of cytogenetics and the application of genetic diagnostic techniques in pathology and hematology. Specifically, the invention relates to nucleic acid probes that can be used in hybridization techniques for the detection of chromosomal aberrations and other gene rearrangements such as immunoglobulin and T-cell receptor gene rearrangements. The probes provided by the invention are a distinct and balanced set of probes of comparable size, each preferably being from 1 to 100 kb, or smaller, and flanking a potential breakpoint in a chromosome.

This invention provides a method of treating cancer or infection by administering T cells transfected with T cell receptors (TCRs) which in their soluble form have a half life for their interaction with their cognate peptide-MHC complex chosen to enhance the avidity of the T cells for target cells presenting that peptide MHC complex while maintaining the activation specificity of the T cells by that peptide-MHC complex.

Disclosed is a method for inducing T cells for immunocytotherapy, the method including (1) a step for providing human pluripotent stem cells with a knocked out Rag1 and / or Rag2 gene, the pluripotent stem cells having a desired antigen-specific T cell receptor gene, and (2) a step for inducing T cells from the pluripotent stem cells of step (1). Further disclosed are immunocytotherapy using T cells for immunocytotherapy, and an iPS cell bank for immunocytotherapy.

The invention provides a method for preparing TCR knockout T cell receptor gene-modified T cells targeting TIPE3, which comprises the following steps: by knocking out the TCR gene on T lymphocytes andpreparing T cell receptors targeting TIPE3, and the TCR knockout T cell receptor gene-modified T cell targeting TIPE3 is obtained. The TCR knockout T cell receptor gene-modified T cell targeting TIPE3 can effectively prevent the mismatch of endogenous and exogenous TCR alpha-chain and beta-chain existing in T cells, autoimmune responses are avoided, and efficient and specific killing performanceof TIPE3 positive tumor cells can be kept. The method also provides an application of TCR knockout T cell receptor gene-modified T cells targeting TIPE3.

The present invention provides a T cell receptor (TCR) capable of specifically binding to an oligopeptide SLLMWITQC derived from an NY-ESO-1 antigen, the antigen oligopeptide SLLMWITQC is capable of forming a complex with HLA A0201 and is presented together to the surface of a cell. The invention also provides nucleic acid molecules encoding the TCR and a vector comprising the nucleic acid molecules. In addition, the invention also provides a cell for transducing the TCR.