790 results about "Cellular receptor" 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.

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.

Embodiments of the invention include compositions and methods related to engineered human mucosal-associated invariant T (eMAIT) cells for off-the-shelf use for clinical therapy for cancer, infectious, and autoimmune diseases. In some embodiments, the eMAIT cells are produced from healthy human donor peripheral blood, cord blood, or G-CSF mobilized peripheral blood. In particular embodiments, the eMAIT cells are produced from a pluripotent stem cell line and therefore can be of unlimited supply. In some embodiments, the eMAIT cells are engineered to express chimeric antigen receptors (CARs), or / and immune regulatory molecules, or / and allorejection resistance molecules. Embodiments of the invention also include compositions of matter comprising polynucleotides encoding mucosal-associated invariant T cell receptor alpha chain polypeptides and / or mucosal-associated invariant T cell receptor beta chain polypeptides.

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 present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

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 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 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.

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.

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 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 disclosure relates to nanoparticles comprising a surface-exposed immune cell binding moiety, a transposable element comprising a gene sequence flanked by inverted terminal repeats (ITRs), a nucleic acid encoding a transposase with specificity for the ITRs, and an mRNA encoding a first chimeric antigen receptor (CAR) or T-cell receptor (TCR). Methods are also described for treating a disease or disorder by administering such nanoparticles to a subject in need thereof.

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).

The invention relates to a chimeric T-cell receptor (TCR) comprising a human transmembrane domain, a human intracellular domain and a human intracellular CD3ε domain wherein in at least one of the CD3ε domains, an arginine (R) amino acid residue at position 53 and / or 54 of SEQ ID NO:25, or an arginine (R) amino acid residue at a position that corresponds to said arginine (R) amino acid residue at position 54 of SEQ ID NO:25, is substituted or deleted. The invention further relates to a method of producing a T-cell expressing the chimeric co-stimulatory TCR. The invention further relates to a chimeric T-cell receptor (TCR) comprising a human co-stimulatory domain and a human CD3ε domain. The invention further relates to a method of treating a patient having a tumor or an immune-related disease comprising administering T-cells expressing the chimeric TCR to the patient.

Provides herein are multifunctional molecules comprising T cell receptor variable beta-binding moieties and cytokines, and methods of treating conditions or diseases in a subject using the same.

Provided herein are compositions comprising trispecific and / or trivalent binding proteins comprising four polypeptide chains that form three antigen binding sites that specifically bind one or more HIV target proteins or one or more T-cell receptors, wherein a first pair of polypeptides forming the binding protein possess dual variable domains having a cross-over orientation and wherein a second pair of polypeptides forming the binding protein possess a single variable domain. Also provided herein are methods for making trispecific and / or trivalent binding proteins and uses of such binding proteins for the treatment and / or prevention of HIV / AIDS.

The present invention relates to specific binding molecules which bind to the HLA-E restricted peptide RLPAKAPLL (SEQ ID NO: 1) derived from Mycobacterium tuberculosis enoyl-ACP reductase. Said specific binding molecules may comprise CDR sequences embedded within a framework sequence. The CDRs and framework sequences may correspond to a T cell receptor (TCR) variable domain and may further comprise non-natural mutations relative to a native TCR variable domain. The specific binding molecules of the invention are particularly suitable for use as novel immunotherapeutic reagents for the treatment of infectious disease.

The present technology provides polypeptides comprising a first immunoglobulin single variable domain (ISVD) binding to albumin, a second ISVD capable of binding to both the constant domain of a human T cell receptor (TCR) on a T cell and the constant domain of a non-human primate TCR on a T cell, wherein said first and second ISVD are linked by a protease cleavable linker, and a targeting moiety. The present technology further provides nucleic acids encoding said polypeptides as well as vectors, hosts and methods to produce these polypeptides. Moreover, the present technology relates to methods for treatment making use of the polypeptides according to the present technology.

The invention relates to WT1 specific and HLA-E restricted TCRs, as well as nucleic acids encoding the TCR and vectors comprising such nucleic acid. The invention also relates to uses of such a TCR in treating or preventing cancer.

The invention discloses a substance composition. The present invention relates to a conjugate comprising a deglycosylated IgA-binding moiety, a cell receptor-binding moiety that binds to a hepatocyte or other degraded cell of a patient or subject through an asialoglycoprotein receptor (ASGPR) on the surface of the hepatocyte or other degraded cell, and optionally a linker moiety that links the deglycosylated IgA-binding moiety and the cell receptor-binding moiety, wherein the composition of matter can be used to remove galactose deficient IgA1 in a patient or subject.

The present disclosure provides T cell receptors (TCRs) that bind to antigenic peptides of MAGE-A10 presented by HLA-A molecules. Also provided are nucleic acids encoding such TCRs, vectors comprising such nucleic acids, cells comprising such TCRs, nucleic acids and vectors, and compositions comprising such TCRs, nucleic acids, vectors, and cells. Also provided are methods for treating diseases / conditions using, and medical uses of, such TCRs, nucleic acids, vectors, cells and compositions.

An antibody against respiratory syncytial virus (RSV) and / or human metapneumovirus (HMPV) is described herein. The antibody includes binding domains from anti-idiotypic monoclonal antibodies (ai-mAbs) that bind an RSV neutralizing antibody VH3-21 / VL1-40 presented as B cell receptors (BCRs). The antibodies can be used as a vaccine to selectively elicit antibodies capable of neutralizing RSV and / or HMPV without a need for somatic mutation. The vaccines are particularly useful to treat and / or reduce the risk of RSV and / or HMPV infection in infants.

The application provides guidance and navigation control (GNC) proteins. In one embodiment, the GNC protein Comprises a T-cell binding moiety and a cancer-targeting moiety, wherein the T-cell binding moiety has a binding specificity to a T-cell receptor comprising CD3, CD28, PDL1, PD1, OX40, 4-1BB, GITR, TIGIT, TIM-3, LAG-3, CTLA4, CD40, VISTA, ICOS, BTLA, Light, NKp30, CD28H, CD27, CD226, CD96, CD112R, A2AR, CD160, CD244, CECAM1, CD200R, TNFRSF25 (DR3), or a combination thereof, and wherein the cancer targeting moiety has a binding specificity to a cancer cell receptor.

Featured are devices, systems, and methods of use for detecting binding of polynucleotide-peptide conjugate-major histocompatibility complex (pMHC) monomers to a T cell receptors (TCR) on a T cell, and the use of a peptide library to detect binding of antigenic peptides in a pMHC monomer to a T cell receptor (TCR) on a T cell.

Intracellular delivery of a genetic construct to immune cells including: obtaining a deterministic mechanoporation (DMP) platform that includes a substrate having a surface and a plurality of capture sites, each said capture site having a boundary shape at the surface adapted and configured to support thereon a cell, and each said capture site having a bottom and including a sub-micron-scale projection extending from the bottom toward the surface of the substrate, wherein said projection is adapted and configured to penetrate a cell membrane and / or wall of the cell, and wherein the substrate has a plurality of aspiration vias situated at the bottom of the capture sites; introducing the cells to the surface in a liquid media; capturing the cells within the capture sites by applying a first hydrodynamic force; applying a second hydrodynamic force on the captured cell and locally rupturing the membrane and / or wall of the cell with the projection, introducing the genetic construct into the cells, and releasing the porated cells from the capture sites. Also disclosed are methods of chimeric antigen receptor (CAR) T cell adoptive immunotherapy and T cell receptor (TCR) therapy.

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.