847 results about "T-cell Antigen" patented technology

The invention provides a specific T cell receptor targeting KRAS G12V mutant epitope peptide (such as an amino acid sequence as shown in SEQ ID NO: 2) and anti-tumor application of the specific T cell receptor. The specific T cell receptor is composed of two peptide chains alpha and beta and can be specifically combined with a VVGAVGVGK-HLA-A * 11: 01 compound. The invention also provides an antigen binding fragment of the specific T cell receptor, a nucleic acid sequence for coding the T cell receptor, a vector containing the nucleic acid sequence, an engineered cell for expressing the T cell receptor, a composition containing the T cell receptor and application thereof. In addition, the invention also provides a method for screening the KRAS G12V specific T cell receptor. The specific T cell receptor and the antigen binding fragment thereof provided by the invention can be used as an immune effect activator to stimulate the immune response of a body, so that the effect of resisting diseases such as tumors and the like is achieved.

The invention relates to the technical field of biological medicine, in particular to a T cell receptor targeting AFP peptide, a preparation method of the T cell receptor and a companion diagnostic kit. A T cell receptor targeting an AFP peptide is provided, the sequence of the AFP peptide is FMNKFIYEI, and the T cell receptor comprises a TCR [alpha] chain variable domain and a TCR [beta] chain variable domain. Corresponding nucleic acid molecules, vectors and host cells, and methods of making T cell receptors are provided. Further provided is a companion diagnostic kit containing the cell receptor. The invention provides a better choice for concomitant diagnosis and treatment products of cells of alpha fetoprotein (AFP).

This disclosure provides methods of increasing in vivo transfection efficiency and pharmacologic activity of T cells, by administering multiple small doses within a compact time period of T cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor that recognizes an antigen of a cell against which immune activity is to be directed. Also provided are methods of depleting B cells, and methods of treating B cell-mediated diseases and disorders by depleting B cells and achieving immunological reset, entailing administration of immune cell-targeted lipid nanoparticles encapsulating mRNA encoding an antigen receptor recognizing a B cell marker as multiple small doses within a compact time period. The antigen receptor can be a T cell receptor or a chimeric antigen receptor.

The invention discloses an anti-TP53 mutation T cell receptor and application thereof, the T cell receptor comprises specific alpha chain and beta chain variable domains, and the complementary determining region (CDR) sequence is shown as SEQ ID NO: 9-14. The TCR has the core advantage that the TCR has excellent broad-spectrum recognition capability, can target six different amino acid substitutions (A, G, I, N, S and T) at the R249 site, and effectively deals with tumor heterogeneity and mutation difference between patients. Aiming at high-frequency HLA-B * 07: 02 alleles in people, the TCR lays a foundation for developing TCR-T cell therapy covering a wide range of people, and has great clinical application value and market potential in treatment of various solid tumors carrying TP53 R249 hotspot mutation, such as liver cancer.

The invention belongs to the technical field of immunotherapy, and particularly relates to a monkey pox virus antigen epitope peptide and application thereof. The invention aims to solve the technical problem that at present, a T cell antigen epitope peptide for universal vaccines of monkey pox viruses is not developed in the field of monkey pox viruses. According to the technical scheme of the invention, the amino acid sequence of the monkey pox virus antigen epitope peptide is shown as SEQ ID No.2. The antigen epitope peptide provided by the invention has very strong immunogenicity, and can induce antigen-specific CD8 + T cells; the antibody can be directly loaded to antigen presenting cells, can activate T cells and effectively induce T cell immunity, and can be used for research and development and preparation of universal vaccines for monkey pox viruses, research and development of drugs and clinical treatment.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

The present invention relates to binding molecules that comprise T cell receptor (TCR) variable domains and which can bind to a PIWIL1 peptide-HLA complex. The invention also relates to the use of such molecules for the treatment of malignant diseases.

The invention discloses a TCR (T cell receptor)-like monoclonal antibody for treating NPM1 type A mutant acute leukemia, which is a recombinant protein pNPM1-HLA protein expressed by SEQ ID NO1 or SEQ ID NO2, the recombinant protein is combined with a monoclonal antibody of pNPM1-HLA-A2, the monoclonal antibody can specifically recognize the combination of the pNPM1-HLA-A2 protein on the surface of a tumor cell, the combination with a non-target peptide / HLA-A2 protein is low, and the monoclonal antibody can be used for treating NPM1 type A mutant acute leukemia. The specific recognition on the tumor cells is realized. The monoclonal antibody provided by the invention has the following advantages: (1) the monoclonal antibody 2E2 has high affinity with a target protein, and Biacore affinity detection KD (M) is 1.58 e <-7 >; and (2) the antibody can be combined with a tumor cell line for expressing pNPM1-HLA-A2. And (3) the modified antibody has an obvious killing effect on tumor cells in vitro and in vivo.

Methods for selecting a cancer patient for immunotherapy comprise establishing a total passenger gene mutation burden from a tumor of a cancer patient, generating a background distribution for the mutational burden of the tumor, normalizing the total passenger gene mutation burden against the background distribution, and categorizing the cancer patient as an immunotherapy responder when the total passenger gene mutation burden is greater than the mean of the background distribution. When the cancer patient is an immunotherapy responder, the patient may be administered an immunotherapy regimen that comprises activation / inhibition of T cell receptors that promote T cell activation and / or prolong immune cytolytic activities.

A monoclonal humanized antibody or antigen-binding fragment thereof that specifically bind to the TRBV9 family of the human T cell receptor. A nucleic acid encoding the antibody or antigen-binding fragment thereof, an expression vector, a method for preparing the antibody, and use of the antibody in treatment of diseases or disorders associated with the human T cell receptor family. The generation of antibodies that can be used for treating, in particular AS, celiac disease and malignant blood diseases, the pathogenesis of which involves the TRBV9 family TCRs.

The invention relates to the technical field of immune repertoire sequencing, in particular to a sequence data analysis method and device for biological system state modeling and a storage medium. According to the method, high-throughput sequencing data of B / T cell receptors are acquired, nonlinear gain correction and V-J gene combination preference feature extraction are performed, structured feature nodes are constructed, features are coded by using a Transform model, a system state vector is generated in combination with weighted average pooling, adversarial training is introduced to realize feature decoupling, and signal interference among functional categories is inhibited. And calculating a multi-dimensional immune intensity score based on the system state vector, and quantifying immune response active degrees of different function categories. According to the method, high-sensitivity and multi-dimensional parallel modeling and dynamic evaluation of the immune system state are achieved, the method is suitable for large-scale population immune monitoring and system biological research, and the analysis capacity and application value of immune group library data are remarkably improved.

The invention belongs to the technical field of biological medicine, and particularly relates to a T cell receptor capable of recognizing KRAS G12V antigen oligopeptide, a compound, a pharmaceutical composition and application. The T cell receptor can be used for recognizing a KRAS G12V-HLA-A * 11: 01 compound with high affinity; the T cell receptor is an alpha-beta heterodimer consisting of an alpha chain and a beta chain; the amino acid sequence of the alpha chain is as shown in SEQ ID NO.10, or an amino acid sequence with at least 90% of sequence identity with the alpha chain; the amino acid sequence of the beta chain is as shown in SEQ ID NO.14, or has an amino acid sequence with at least more than 90% of sequence identity with the beta chain. The T cell receptor provided by the invention can be used for preparing medicines for treating tumors or other immune diseases.

The invention relates to the technical field of nano-drug presentation systems, in particular to a TCR (T cell receptor) nano-vesicle antibody with both T cell redirection and immunosuppression reversal as well as a preparation method and application of the TCR nano-vesicle antibody. The TCR nano-vesicle antibody comprises a vesicle formed by a liposome and a cell membrane; tCR protein, a PD-1 antibody and a CD3 antibody are loaded on the vesicles. The nano vesicle antibody has the functions of T cell redirection and immunosuppression reversion; the difficulty of low stability of the soluble TCR is overcome; the polypeptide can be rapidly enriched in tumor tissues through tumor specificity TCR, and CD8 + T cells infiltrated by tumors are directly activated through an anti-CD3 antibody; depletion of T cells can be reversed through the PD-1 antibody on the surface, and the effector function of tumor infiltration CD8 + T cells is improved. The technical scheme can solve the technical problems that the TCR stability is not ideal and the immunosuppression state of the tumor microenvironment is difficult to overcome, and has ideal application and popularization prospects.

The invention provides a CD4 + T cell receptor and polypeptide combination prediction method and prediction system based on deep learning. The prediction method comprises the following steps: respectively obtaining TCR sequence features and polypeptide sequence features based on a CD4 + TCR sequence and a polypeptide sequence, and fusing the TCR sequence features and the polypeptide sequence features to obtain fused sequence features; obtaining TCR descriptor features and polypeptide descriptor features based on the CD4 + TCR sequence and the polypeptide sequence, and fusing the TCR descriptor features and the polypeptide descriptor features to obtain fused descriptor features; obtaining TCR spatial characteristics and polypeptide spatial characteristics based on the CD4 + TCR sequence and the polypeptide sequence, and fusing the TCR spatial characteristics and the polypeptide spatial characteristics to obtain fused spatial characteristics; and predicting the binding force based on the fusion sequence features, the fusion descriptor features and the fusion spatial features. Therefore, the accuracy of combination prediction of the CD4 + T cell receptor and the polypeptide can be improved.

The present invention provides multispecific antibodies comprising a Fab region and an Fc region, wherein the Fab region comprises a binding site specific for an epitope of the variable delta 1 (Vδ1) chain of a γδ T cell receptor (TCR); and the Fc region comprises an EGFR binding site. The present invention also provides compositions and pharmaceutical compositions comprising such multispecific antibodies, and method of making such multispecific antibodies. The present invention also provides methods of treatment and medical uses involving the multispecific antibodies.

The invention relates to a method for screening a human-mouse cross MR1 restriction high-affinity TCR (T cell receptor) by using a phage display technology, and relates to the technical field of T cell receptors. According to the invention, a phage display technology is utilized to prepare an MAIT cell single-chain T cell receptor (scTCR) phage library, the scTCR phage library is subjected to biological elutriation through an MR1 / 5-OP-RU tetramer, and Phage-ELISA identifies that TCR6 clone (TCR6) has specific binding with human and mouse MR1 / 5-OP-RU and has higher affinity compared with other clone.

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.

The present disclosure provides gene edited modified immune cells or precursors thereof (e.g., gene edited modified T cells) comprising an exogenous T cell receptor (TCR) and / or a chimeric antigen receptor (CAR) having specificity for a target antigen, and an insertion and / or deletion in one or more endogenous gene loci, wherein the endogenous gene loci encode regulators of T cell function, thereby resulting in immune cells having enhanced function. Compositions and methods of treatment are also provided. The present invention provides methods of screening for TCR- or CAR-T cells with enhanced immune function (e.g., T cell efficacy, T cell memory, and / or T cell persistence).

Provided is a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs disclosed herein. Aspects of the disclosure relate to a polynucleotide encoding a chimeric antigen receptor (CAR) or a T cell receptor (TCR) comprising one or more of the antigen binding motifs. Provided are antibodies and antigen binding systems that comprise a binding motif that binds CD20 and optionally a binding motif that binds CD19, and methods of producing and using the same. Antibodies and antigen binding systems of the present disclosure comprise CARs that comprise an anti-CD20 binding motif and an anti-CD19 binding motif. Provided are compositions, such as antibodies and CARs that are or comprise an anti-CD20 / anti-CD19 antigen binding system of the present disclosure, and cell therapies comprising the same, are useful, e.g., in the treatment of cancer.

The invention discloses a TCR (T cell receptor) for identifying MAGE-A3 and application thereof, the TCR comprises an alpha chain and / or a beta chain, and the alpha chain or the beta chain comprises a CDR amino acid sequence or a variable region amino acid sequence described in any one of SEQ ID NO.1-48. The invention also discloses a bispecific TCR, a recombinant TCR, a nucleic acid molecule, a vector, an engineered cell and a composition.

Disclosed herein are non-human animals (e.g., rodents, e.g., mice or rats) genetically engineered to express a human or humanized T cell receptor (TCR) from a human or humanized TCR locus comprising a non-human TCR non-coding sequence, and optionally a humanized T cell co-receptor (e.g., humanized CD4 and / or CD8 (e.g., CD8α and / or CD8β)), 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 the genetically engineered animals are also provided. Methods for using the genetically engineered animals for developing human therapeutics are also provided.

The invention discloses a gene-edited tumor infiltrating lymphocyte and a T cell receptor engineered T cell and application thereof in immunotherapy. According to the invention, NR4A1 and / or NR4A2 and / or NR4A3 genes are / is knocked out from tumor infiltrating lymphocytes or T cell receptor engineered T cells, so that the multiplication capacity and the anti-tumor capacity of the tumor infiltrating lymphocytes or T cell receptor engineered T cells are improved.

The present disclosure relates to T cells capable of co-expressing T cell receptors (“TCR”) together with CD8 polypeptides and the use thereof in adoptive cellular therapy. The present disclosure further provides for modified CD8 sequences, vectors, and associated methods thereof.

The present invention relates to an isolated T cell receptor (TCR) specific for MAGE-A4 and a polypeptide comprising a functional portion of the TCR. Further implicated are a multivalent TCR complex, a nucleic acid encoding a TCR, a cell expressing the TCR and a pharmaceutical composition comprising the TCR. The invention also refers to the TCR for use as a medicament, in particular to the TCR for use in the treatment of cancer.

The invention relates to the technical field of biological medicine, in particular to a T cell receptor targeting PRAME peptide and a preparation method of the T cell receptor. Specifically, the invention also provides a T cell receptor, a corresponding nucleic acid molecule, a vector, a host cell and a method for preparing the T cell receptor, and the TCR-T cell obtained by the invention can effectively treat melanoma specific antigen (PRAME) positive tumors and provide more treatment options for patients.

The present disclosure is directed recombinant T cell receptors capable of binding a gp100 epitope and nucleic acid molecules encoding the same. In some embodiments, the nucleic acid molecules further comprise a second nucleotide sequence, wherein the second nucleotide sequence or the polypeptide encoded by the second nucleotide sequence inhibits the expression of an endogenous TCR. Other aspects of the disclosure are directed to vectors comprising the nucleic acid molecule and cells comprising the recombinant TCR, the nucleic acid molecule, or the vector. Still other aspects of the disclosure are directed to methods of using the same. In some embodiments, the methods comprise treating a cancer in a subject in need thereof.

An isolated cell having a central memory T-lymphocyte (Tcm) phenotype, the cell being tolerance-inducing cell and capable of homing to the lymph nodes following transplantation, the cell being transduced to express a cell surface receptor comprising a T cell receptor signaling module is described. Methods of generating same and using same are also described.

The invention relates to an antibody composition for detecting abnormal CTL (cytotoxic T lymphocyte) cells of hemophagocytic syndrome and application of the antibody composition, and the antibody composition comprises a CD2 antibody, a CD3 antibody, a CD4 antibody, a CD5 antibody, a CD7 antibody, a CD8 antibody, a CD56 antibody, a CD57 antibody, a Granzyme B antibody, a Perforin antibody, a TRBC1 antibody and a CD45 antibody. In the technical scheme provided by the invention, key phenotypic characteristics of CTL (Cytotoxic Lymphocyte) can be completely covered by various antibodies aiming at T cell and NK cell surface markers, T large granular lymphocyte markers, cytotoxic granular proteins, T cell receptor constant regions and leukocyte common antigens; wherein the clonality of the CTL cells is judged through the expression level of the TRBC1 antibody, and the cytotoxic function activity of the CTL cells is evaluated through the expression levels of Granzyme B and Perforin.

The invention relates to the technical field of biological medicine, in particular to a T cell receptor targeting AFP peptide, a preparation method of the T cell receptor and a companion diagnostic kit. A T cell receptor targeting an AFP peptide is provided, the sequence of the AFP peptide is FMNKFIYEI, and the T cell receptor comprises a TCR [alpha] chain variable domain and a TCR [beta] chain variable domain. Corresponding nucleic acid molecules, vectors and host cells, and methods of making T cell receptors are provided. Further provided is a companion diagnostic kit containing the cell receptor. The invention provides a better choice for concomitant diagnosis and treatment products of cells of alpha fetoprotein (AFP).

A series of recombinant DNA constructs and a method is disclosed for use in immunological therapy in general; and in disrupting T cell receptor (TCR), human leukocyte antigens (HLA) class I and NKG2D (Natural-Killer Group 2, member D) ligand expression in particular, with the effect of producing highly compatible autologous universal T cells for further genetically engineering for allogeneic administration. A Universal T (UT) construct is provided and used, comprising a TCR antibody fragment fused to a transmembrane domain (TMD) and ER retention domain of adenovirus early region 3 glycoprotein E3-19k (E3 / 19K) (TCR-E3 / 19K RD). The Universal T (UT) construct can hijack ERAD machinery to arrest TCR and HLA molecules in endoplasmic reticulum (ER) and facilitate their translocation into the cytoplasm for ubiquitination and degradation by proteasomes.