1103 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.

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.

Transgenic rodents and rodent cells that express components of the human immune system, and their uses in generating human T cell receptors (TCRs). A genetically modified rodent comprising a TCR alpha gene locus comprising unrearranged human TCR alpha variable gene segments and a human TCR alpha constant region, and a TCR beta gene locus comprising unrearranged human TCR beta variable gene segments and a human TCR beta constant region. Use of hTCR transgenic rodents to generate antigen-specific CD8+ T cell responses for the discovery of fully human TCR sequences with therapeutic potential.

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 application provides a bispecific antibody comprising a first antigen binding fragment that binds to an HLA-A24 / PRAME complex and a second antigen binding fragment that binds to an activated T cell antigen, a single domain antibody that binds to an HLA-A24 / PRAME complex, a pharmaceutical composition comprising the bispecific antibody or the single domain antibody, and uses thereof.

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 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 a monoclonal humanized antibody or antigen-binding fragment thereof that specifically bind to the TRBV9 family of the human T cell receptor. The invention also relates to a nucleic acid encoding said antibody or antigen-binding fragment thereof, an expression vector, a method for preparing said antibody, and use of said antibody in treatment of diseases or disorders associated with the human T cell receptor family. The invention is directed to 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 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.

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 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 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.

This invention relates to modified T cells that inducibly express a bioactive molecule, such as IL-7, and constitutively expresses an antigen receptor, such as a T cell receptor or chimeric antigen receptor that binds to a tumour antigen. The modified T cells may comprise a nucleic acid construct that comprises a first nucleotide sequence encoding the bioactive molecule, a second nucleotide sequence encoding the antigen receptor; an inducible promoter operably linked to the first nucleotide sequence and a constitutive promoter operably linked to the second nucleotide. Nucleic acid constructs and vectors are provided, as well as T cells comprising such constructs and vectors and therapeutic methods and uses thereof.

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.

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.

The present disclosure provides compositions and methods for targeting SOX2 antigen to, for example, treat or manage cancer. Provided compositions include binding proteins that are capable of binding to a SOX2 antigen:HLA complex. Also provided are polynucleotides and transgene constructs encoding binding proteins, such as a T cell receptor or a chimeric antigen receptor, that specifically bind to a SOX2 antigen. Such polynucleotides and transgene constructs can be introduced into an immune cell, such as a T cell, and used in immunotherapy in a subject having or at risk for a cancer associated with SOX2 expression or activity. The present disclosure also provides immunogenic compositions comprising SOX2 antigens, and related uses.

The present application provides a bispecific antibody comprising a first antigen binding fragment that binds to an HLA-A02 / MAGE-A4 complex and / or an HLA-A02 / MAGE-A8 complex and a second antigen binding fragment that binds to an activated T cell antigen, a single domain antibody that binds to an HLA-A02 / MAGE-A4 complex and / or an HLA-A02 / MAGE-A8 complex, and a method for preparing the same. The invention also relates to a pharmaceutical composition containing the bispecific antibody or the single-domain antibody and application of the bispecific antibody or the single-domain antibody.