973 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.

The invention provides a composition capable of penetrating an intestinal barrier by oral administration. The composition contains a carrier or an auxiliary material of a targeted Microflod cell Dectin-1 receptor, and one or / and a plurality of medicinal components / components, wherein the carrier or the auxiliary material of the target Microflood cell Dectin-1 receptor is beta-glucan, and the carrier or the auxiliary material of the target Microflood cell Dectin-1 receptor is beta-glucan. The effective components / components are traditional Chinese medicine effective components / components, or / and probiotics, or / and chemical medicine components, or / and biological medicines. The invention relates to a composition capable of realizing oral administration and penetrating through an intestinal barrier, which is based on the discovery of the inventor that the composition reaches colon through gastrointestinal tracts, targets colon Microflood cells, is taken by the Microflood cells, penetrates through the intestinal barrier and enters immune tissue Colonic Patches of a colon submucosa. Based on the research, the composition disclosed by the invention can be used for treating various diseases, such as ulcerative colitis, Crohn's disease, colon cancer, rheumatoid arthritis or bacterial pneumonia after being orally taken and absorbed by rectum.

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.

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.

The invention discloses a T cell receptor-epitope binding specificity prediction method based on multilevel knowledge distillation, and relates to a T cell receptor-epitope binding specificity prediction method. The method aims to solve the problem that an existing deep learning model is poor in performance when generalized to be free of epitopes. The feature extraction module is constructed by using the convolutional neural network, and the interaction mode between the TCR and the epitope is explored through a bilinear attention mechanism. Thirdly, internal multi-feature knowledge distillation and inter-domain knowledge distillation are carried out, knowledge is extracted from multiple teacher models, and the predictive ability of student models is enhanced; tCR-epitope pairs in a training set are input into the model, and the model is trained; after multiple iterations, a final prediction model is obtained; and inputting the TCR-epitope pair in the test set into the final prediction model to obtain a prediction result, and performing result analysis. The invention belongs to the technical field of biological information.

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.

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.

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.

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 the field of immunity, in particular to a T cell receptor with improved affinity, a nucleic acid molecule, a carrier, a cell and a medicine containing the T cell receptor, the nucleic acid molecule, the carrier and the cell for treating tumors. The T cell receptor includes a TCR [alpha] chain variable region and a TCR [beta] chain variable region, which have activity to bind to a KRAS G12V epitope and an HLA-A * 11 complex, and the TCR [alpha] chain variable region includes CDR1 [alpha], CDR2 [alpha] and CDR3 [alpha] complementarity determining regions, and the TCR [beta] chain variable region includes CDR1 [beta], CDR2 [beta] and CDR3 [beta] complementarity determining regions. The TCR provided by the invention has high-affinity target antigen peptide binding capacity, remarkably improves the target cell recognition capacity, shows good activation and killing activity, and shows high technical value and clinical application potential.

The invention relates to a TCR and / or BCR detection system based on spatial omics, and aims to solve the problems of high detection cost, low spatial resolution, incapability of accurately positioning cells and the like in the existing spatial VDJ technology. The invention provides a T cell receptor and / or B cell receptor detection system based on a spatial omics method, the system comprises: a module (1), which constructs a coding primer pool according to a VJ region sequence of TCR and / or BCR to be detected, the VJ region is formed by rearranging a V region and a J region, the coding primer pool is used for each V region and J region to be detected, and the coding primer pool is used for coding the TCR and / or BCR to be detected. Or specific coding sequences are distributed to the V region and the CDR3 region respectively; the module (2) is used for amplifying a to-be-detected VJ region of a to-be-detected tissue sample through the coding primer pool and fixing an amplification product; and the module (3) is used for positioning the amplification product by using the signal probe group and reading the coding sequence, so that the position information of the VJ region is obtained, and the sequence information of the VJ region is obtained according to the coding sequence.

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.

Tropomyosin-related kinase inhibitors (Trk inhibitors) are small molecule compounds useful in the treatment of disease. Trk inhibitors can be used as pharmaceutical agents and in pharmaceutical compositions. Trk inhibitors are useful in the treatment of inflammatory diseases, autoimmune disease, defects of bone metabolism and / or cancer, and are particularly useful in the treatment of osteoarthritis (OA), pain, and pain associated with OA. Trk inhibitors are also useful for inhibiting tropomyosin-related kinase A (TrkA), tropomyosin-related kinase B (TrkB), tropomyosin-related kinase C (TrkC), and / or c-FMS (the cellular receptor for colony stimulating factor-1 (CSF-1)).

The present disclosure provides compositions and methods for targeting neoantigens, for example, to treat or prevent cancer. The disclosed embodiments include binding proteins, such as T cell receptors, that bind to the neoantigen: HLA complex. The binding protein further comprises a construct comprising a fusion protein of the CD95 extracellular domain and the CD137 intracellular signaling domain (Fas-41BB), and a CDS coreceptor alpha or beta chain. The disclosed binding proteins are highly sensitive to antigens and are capable of inducing activation of host T cells at low concentrations of peptide antigens. In certain embodiments, binding proteins of the present disclosure (i) have no alloreactivity, substantially no alloreactivity, and / or low risk of alloreactivity, to amino acid sequences from human proteomes and / or (ii) to human HLA alleles. Polynucleotides encoding such binding proteins can be introduced into host cells, such as T cells, and the cells can be used in immunotherapy for the treatment of various cancers.

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 provides compositions and methods for targeting a Ras antigen to, for example, treat or prevent cancer. Disclosed embodiments include binding proteins, such as a T cell receptor or a chimeric antigen receptor, that bind to a Ras antigen:HLA complex. Polynucleotides encoding such binding protein can introduced into a host cell, such as a T cell, and the cell can be used in immunotherapy for treating various cancers. Also provided are immunogenic polypeptides that can be useful to, for example, induce an immune response against a mutated Ras or to identify a binding protein that binds to a Ras antigen.

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 present invention relates to monoclonal humanized antibodies or antigen-binding fragments thereof that specifically bind to the TRBV9 family of human T-cell receptors. The present invention also relates to nucleic acids encoding said antibodies or antigen-binding fragments thereof, expression vectors, methods for preparing said antibodies and the use of said antibodies in the treatment of diseases or disorders associated with said family of human T-cell receptors. The present invention relates to the production of antibodies that can be used to treat, inter alia, ankylosing spondylitis (AS or Bechterev's disease), celiac disease and blood cancers, whose pathogenesis involves T-cell receptors of the TRBV9 family.

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.