2454 results about "Antigen receptor" patented technology

Recombinant NK cells, and especially recombinant NK-92 cells express a chimeric antigen receptor (CAR) having an intracellular domain of FcεRIγ. Notably, CAR constructs with an intracellular domain of FcεRIγ had a substantially prolonged duration of expression and significantly extended cytotoxicity over time. The CAR may be expressed from RNA and DNA, preferably as a tricistronic construct that further encodes CD16 and a cytokine to confer autocrine growth support. Advantageously, such constructs also enable high levels of transfection and expression of the recombinant proteins and provide a convenient selection marker to facilitate rapid production of recombinant NK / NK-92 cells.

The invention discloses a CA9-targeted chimeric antigen receptor and application thereof, and belongs to the technical field of biological medicines. The CA9 targeting chimeric antigen receptor provided by the invention comprises a CD8 alpha leading signal peptide, an anti-CA9 single-chain variable fragment, a CD8 alpha hinge, a CD8 transmembrane structural domain and a CD3 zeta intracellular costimulatory signal transduction structural domain. According to the invention, an anti-CA9 single-chain variable fragment is used as an antigen binding structural domain to construct a chimeric antigen receptor (CAR) molecule, the macrophage expressing the anti-CA9CAR can realize specific targeting and phagocytosis killing of CA9 positive kidney cancer cells, and the constructed lipid nanoparticle delivery system can effectively transfer a gene expression vector, so that the gene expression vector can realize effective target site delivery, and the CA9 positive kidney cancer cells can be effectively targeted and killed. The constructed hydrogel-liposome combined drug delivery system has the performance of relieving toxic and side effects, controllable release and hemostasis.

The invention belongs to the technical field of biology, and provides a nanometer antibody targeting Nectin-4, and a nucleic acid molecule and an expression vector for coding the nanometer antibody targeting Nectin-4. The invention also provides a chimeric antigen receptor which comprises an extracellular antigen binding domain, a transmembrane domain and an intracellular domain, and the extracellular antigen binding domain is a Nectin-4 nano antibody; the invention also provides a chimeric antigen receptor CAR which contains the nano antibody as scFv and co-expresses CXCR1, a CAR-T cell constructed by the chimeric antigen receptor CAR, and an enhanced CAR-T cell obtained by modifying the CAR-T cell with microbial short-chain fatty acid, so as to improve the infiltration and anti-tumor activity of the CAR-T cell targeting Nectin-4.

Various embodiments of the invention provide binding molecules for B-lymphocyte antigen (e.g., CD 19 and CD20), including antigen recognizing receptors (e.g., CARs) that target B-lymphocyte antigens (e.g., CD 19 and CD20). Embodiments of the invention also provide cells expressing such binding molecules, therapeutics compositions comprising such cells, and methods for treating diseases or disorders associated with B-lymphocyte antigen (e.g., CD19 and CD20), including a hematologic cancer, an autoimmune disease (e.g., multiple sclerosis and systemic lupus erythematosus).

The invention relates to an anti-DLL3 nano antibody, a chimeric antigen receptor and application of the anti-DLL3 nano antibody and the chimeric antigen receptor. Specifically, the invention provides a nano antibody specifically binding to DLL3 or an antigen binding fragment thereof, provides a chimeric antigen receptor related to the nano antibody or the antigen binding fragment thereof, a polynucleotide, a recombinant vector, a host cell, an antibody, an antibody conjugate, a pharmaceutical composition and a kit, and also provides related uses and methods.

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 includes improved methods and compositions for detecting specific insertion of a chimeric antigen receptor (CAR) sequence in the desired locus in the genome of a cell. Methods are useful as quality control for CAR-T cell or CAR-NK cell preparations.

The use of dual-target CAR-T cells in treating systemic lupus erythematosus and other B-cell autoimmune diseases is provided. The first target of the chimeric antigen receptor is CD19, the second target is BCMA, and specifically, the chimeric antigen receptor is a chimeric antigen receptor with a Loop structure, which is shown as follow: L-VL, CD19-VH, BCMA-VL, BCMA-VH, CD19-H-TM-C-CD3ζ; the BCMA-CD19 CAR-T cells transduced by the chimeric antigen receptor targeting CD19 and BCMA can completely block the pathway of producing autoantibodies, and completely cover the B cells, plasmablasts and plasma cells at multiple differentiation stages that produce autoantibodies, so that the dual-target CAR-T therapy designed based on this concept can be aimed at refractory SLE and is expected to achieve faster remission and deeper and lasting curative effect.

The present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

The invention relates to a method for evaluating the specific killing ability of engineered natural killer cells. Specifically, the invention provides a method for dynamically detecting the killing ability of the immune effector cell in real time, a target cell capable of stably expressing fluorescent protein is constructed, and the real-time killing of the immune effector cell on the target cell is accurately reflected through the disappearance condition of a fluorescence signal of the target cell. In the system provided by the invention, target cells can be added again for continuous challenge, tumor invasion is simulated, and the in-vitro killing function of the natural killer cells of the chimeric antigen receptor is comprehensively evaluated. The method provided by the invention provides effective and accurate evaluation for process development of immune effector cells, especially engineered and modified NK cell products, and provides effective analysis support for researching immune curative effects of NK cells and the like.

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with chronic lymphocytic leukemia (CLL). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods involve prior administration of a lymphodepleting therapy, such as prior administration of fludaribine and / or another lymphodepleting chemotherapeutic agent, for example cyclophosphamide. In some embodiments, features of the methods include an increase in complete remission, overall survival and / or progression free survival of subjects treated in accord with the provided methods.

The invention discloses an artificial antigen presenting cell for efficiently preparing a chimeric antigen receptor T cell (CAR-T) and a construction method of the artificial antigen presenting cell, and belongs to the field of cell therapy and immunotherapy, the artificial antigen presenting cell takes a K562 cell as a platform, an anti-CD3 single-chain antibody, an anti-CD28 single-chain antibody, a membrane binding type cell factor and a costimulatory ligand are stably expressed through genetic engineering, and the chimeric antigen receptor T cell (CAR-T) is obtained. And the local concentration of the anti-CD3 antibody is improved by adopting an HOTag3 tool. The multi-signal integration strategy obviously enhances the activation and proliferation capacity of the T cells, promotes the CAR-T cells to maintain a low differentiation state, and endows the CAR-T cells with excellent anti-tumor activity and durability. The artificial antigen presenting cell provides a novel efficient tool for the field of cellular immunotherapy, and is expected to promote development of more efficient and safer CAR-T therapy to cope with challenges of various malignant tumors.

Disclosed are systems and methods for improving processes for developing cell therapies by applying machine learning to data including manufacturing process data and clinical measurements (e.g., patient response and treatment data) to determine parameters and settings for a manufacturing process for engineering cells for use in cell therapy. Parameters and settings for a manufacturing process for genetically engineered T-cells including, but not limited to, Chimeric Antigen Receptor (CAR) T cells can be determined. A method can include receiving a set of process parameters of a cell engineering process, predicting a clinical response associated with an output of the cell engineering process by applying a machine learning model on the received set of process parameters, where the machine learning model is trained on process parameter data and clinical response data, and generating a visualization for use in a graphical user interface of the predicted clinical response.

The invention discloses a Trop2 targeting chimeric antigen receptor macrophage as well as a preparation method and application thereof. The macrophage contains a specific CAR (chimeric antigen receptor) targeting Trop2 and a blocking agent for blocking an immunosuppression signal; the amino acid sequence of the Trop2 specific CAR targeting the breast cancer is as shown in SEQ ID NO. 1; the nucleotide sequence of the mRNA of the specific CAR of the targeted Trop2 is as shown in SEQ ID NO. 2. According to the invention, LNP is adopted to co-deliver CAR mRNA and TLR agonists, and macrophages are edited in vivo to generate CAR-macrophages expressing Trop2 in situ, so that a tedious engineering cell in-vitro preparation process is omitted, and potential whole-body toxic and side effects caused by immune cell system reinfusion are avoided.

The invention discloses preparation and application of a targeting LYPD3 chimeric antigen receptor T cell. The chimeric antigen receptor comprises an LYPD3 antigen binding domain, a transmembrane domain, a costimulatory signal transduction domain and an intracellular signal transduction domain, the LYPD3 antigen binding domain comprises a heavy chain variable region with CDR-H1, CDR-H2 and CDR-H3 and a light chain variable region with CDR-L1, CDR-L2 and CDR-L3, and the CDR-H1, the CDR-H2 and the CDR-H3 are respectively composed of amino acid sequences of SEQ ID NO: 3, SEQ ID NO: 4 and SEQ ID NO: 5. And the CDR-L1, the CDR-L2 and the CDR-L3 are respectively composed of amino acid sequences as shown in SEQ ID NO: 6, SEQ ID NO: 7 and SEQ ID NO: 8.

The invention relates to the technical field of immunotherapy, and provides a GPRC5D-targeted single-domain antibody, a chimeric antigen receptor and application of the GPRC5D-targeted single-domain antibody and the chimeric antigen receptor. Specifically, the invention provides a GPRC5D-targeted single-domain antibody, a GPRC5D-targeted chimeric antigen receptor (CAR) constructed by using the single-domain antibody, and an engineered immune effector cell containing the CAR. The invention also provides a single-domain antibody targeting GPRC5D, a chimeric antigen receptor and an application of the engineered immune effector cell containing the CAR in preparation of drugs for diagnosis, prevention and / or treatment of diseases or symptoms related to GPRC5D expression.

The invention provides a CAR-NK cell for knocking out KIR2DL5 targeting HER2 as well as a preparation method and application of the CAR-NK cell, and belongs to the technical field of genetic engineering.The CAR-NK cell is obtained by adopting a chimeric antigen receptor with HER2 as a target spot to infect an NK cell and then knocking out a KIR2DL5 gene; the chimeric antigen receptor taking the HER2 as the target spot comprises an HER2 single-chain antibody; the nucleic acid artificial sequence of the HER2 single-chain antibody is as shown in SEQ ID NO. 2. According to the application disclosed by the invention, the interaction of KIR2DL5-PVR is blocked by knocking out NK cell immune checkpoints, so that tumor immune escape is avoided, and the activity of killing tumor cells by CAR-NK cells is remarkably enhanced; according to the invention, by optimizing the nucleic acid artificial sequence of HER2, the secretion ability of CAR-NK cell factors, the tumor killing efficiency and the in-vivo inhibition effect on tumors can be improved.

The invention provides a bispecific antibody and a chimeric antigen receptor (CAR) which are targeted to BCMA and GPRC5D. The invention also provides a nucleic acid molecule for coding the bispecific antibody and the chimeric antigen receptor, an expression vector containing the nucleic acid molecule, and a cell for expressing the bispecific antibody and the chimeric antigen receptor. The invention also relates to application of the bispecific antibody and the chimeric antigen receptor in disease treatment, in particular to application in treatment of multiple bone marrow cancer.

The invention provides methods of making immune effector cells (e.g., T cells, NK cells) that can be engineered to express a chimeric antigen receptor (CAR), compositions and reaction mixtures comprising the same, and methods of treatment using the same.

A fibroblast activation protein (FAP) targeting chimeric antigen receptor macrophage and its construction method and application. The expression of FAP increases in senescent cells of various senescent diseases. Immune cells, especially macrophages, specifically eliminates senescent cells after expressing chimeric antigen receptor recognizing FAP protein, thereby reducing the pathogenic effect of senescent cells. Macrophages expressing the FAP chimeric antigen receptor can undergo M2-type polarization, which do not produce inflammatory factors to deteriorate age related diseases, have good infiltration ability to tissues with dense matrix, do not induce graft-versus-host disease and have high recognition efficiency of senescent cells and good phagocytic effect. This provides a new idea for preparing reagents for eliminating senescent cells, which have wide potential in practical application.

Provided are nucleic acids that encode decoy-resistant interleukin 18 (DR-18) polypeptides, as well as vectors and cells comprising such nucleic acids and cells that comprise such vectors. Cells encoding DR-18 polypeptides may be referred to as DR-18 armored cells. The nucleic acids may further encode a chimeric antigen receptor (CAR) or multiple CARs, including CARs that bind to antigens described herein. Methods are also provided, including methods of making the nucleic acids, vectors, and / or cells, as well as methods of use, such as employing the nucleic acids, vectors, and / or cells, in the treatment of a subject having cancer.

The present disclosure provides CARs comprising a human mesothelin (MSLN) binder, related polynucleotides and vectors, engineered cells, pharmaceutical compositions, and cell therapies.

The invention relates to the field of medical detection, and particularly provides a diagnostic model for predicting prognosis of gastric cancer CAR-T cellular immunotherapy and application of the diagnostic model. According to the present invention, the content and the spatial distribution map of the CLDN18.2 positive gastric cancer tissue sample microenvironment component are systematically analyzed by integrating the multiple fluorescence immunohistochemical detection and the full-slice digital imaging quantitative analysis method for the first time; through multi-dimensional evaluation of a tumor microenvironment under the treatment background of a targeted CLDN18.2 chimeric antigen receptor T cell immunotherapy CT041, a diagnosis model for predicting the prognosis of the gastric cancer CAR-T cell immunotherapy is established for the first time, accurate screening of benefited people and risk stratification before treatment are realized, treatment selection is guided, and the treatment effect is improved.

The invention discloses a group of anti-human GPC3 nano antibody mutants, a chimeric antigen receptor and application, and belongs to the technical field of immunity. The invention provides a group of anti-GPC3 nano antibody mutants which are used for mutating an existing anti-CPG3 nano antibody (NH3), so that the affinity of the antibody is improved. A chimeric antigen receptor is constructed on the basis of the nano antibody mutant, meanwhile, double-stranded DNA of the nano antibody mutant is synthesized to serve as a template for producing mRNA through in-vitro transcription, and then genetic engineering modification is conducted on NK cells through mRNA, so that the CAR-NK cells are obtained. In the CAR-NK cell disclosed by the invention, mRNA can effectively express CAR molecules on the NK cell, and the CAR-NK cell has stronger in-vitro killing ability and shows a better anti-liver cancer effect.

The invention discloses construction and application of a targeted exosome chimeric antigen receptor molecule for treating HIV (human immunodeficiency virus) infection, and belongs to the technical field of biological medicines. According to the invention, the mRNA for coding the anti-HIV CAR is directionally packaged into the targeting exosome. Nanometer antibody sequences of CD3, CD4 and CD8 < + > T receptors on targeted T cells are fused to the N terminal of LAMP-2B to construct a specific targeting plasmid, so that targeting peptides are expressed on the surface of an exosome membrane, expression plasmids containing RNA binding protein L7A and exosome tag protein CD63 are constructed, and HEK293F cells are co-transfected by the expression plasmids and CAR plasmids containing C / D box to obtain the exosome loaded with CAR mRNA and targeted to the T cells. When the exosome is incubated with PBMC (peripheral blood mononuclear cells) in vitro or is transfused back into a humanized mouse body, human CAR-T cells can be constructed, and the exosome has remarkable activity of killing virus infected cells.

The invention provides a CLDN6 single domain antibody and a humanization method thereof. The CLDN6 single-domain antibody provided by the invention has targeted specificity to CLDN6, only recognizes the CLDN6 and does not recognize CLDN3, CLDN4 and CLDN9 of the same family, or the recognition modes are obviously different. The CLDN6 single-domain antibody 1H07 with targeting specificity provided by the invention can be used for constructing a chimeric antigen receptor (CAR) and a bivalent antibody (bispecific antibody). The CAR constructed based on the antibody sequence can be transduced into a T cell to create a CAR-T cell specifically targeting CLDN6, and the CAR-T cell can be used for treating solid tumors such as ovarian cancer.

As described below, the present disclosure features polypeptides capable of binding a cluster of differentiation 5 (CD5) antigen and polynucleotides encoding said CD5-binding polypeptides, compositions comprising the same, and methods for use thereof. The disclosure also features lipid nanoparticles comprising the CD5-binding polypeptides and methods for use thereof for delivery of a polynucleotide (e.g., a polynucleotide encoding a chimeric antigen receptor) to a T cell in vivo.

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.

A cancer therapy comprising both a population of genetically engineered T cells expressing chimeric antigen receptors (CARs) and a population of antigen presenting cells (APCs) that enhance the efficacy of the T cells expressing the CARs.

The present invention relates to a bispecific chimeric antigen receptor targeting CD117 and CD7 and its application, wherein the bispecific chimeric antigen receptor comprises a signal peptide, an antigen binding domain, a hinge region, a transmembrane domain and a signal transduction domain, wherein the antigen binding domain comprises a CD117 binding domain and a CD7 binding domain. The bispecific chimeric antigen receptor provided by the present invention combines targeted antibodies for CD117 and CD7 together, recognizes and binds to two different antigens at the same time, enhances the targeted elimination ability of malignant cells, and by acting on hematopoietic stem cells and immune cells at the same time, can more effectively eliminate tumor cells in the receptor, while retaining or reconstructing normal hematopoietic and immune functions.