1607 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.

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).

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.

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.

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 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.

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 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 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.

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 discloses a double-target chimeric antigen receptor for co-expression of CD47 and IL-15, a CAR-T cell and application of the CAR-T cell, and belongs to the technical field of genetic engineering, the double-target chimeric antigen receptor comprises a single-chain antibody scFv-EGFRv III, a single-chain antibody scFv-VEGF, CD47 and IL-15; the nucleotide artificial sequence of the single-chain antibody scFv-EGFRv III is as shown in SEQ ID NO. 6; the nucleotide artificial sequence of the single-chain antibody scFv-VEGF is as shown in SEQ ID NO. 9. According to the application disclosed by the invention, by performing sequence optimization on targets EGFRvIII and VEGF, the anti-tumor effect of CAR-T cells in glioblastoma can be improved, and by integrating immune checkpoint molecules CD47 and interleukin-15, the immunosuppression function of a CD47-SIRP alpha signal channel can be locally exerted.

Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-β ligand or a TGF-β receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and / or through engagement of a TGF-β ligand or a TGF-β receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Provided herein are chimeric receptors, including chimeric antigen receptors (CARs), comprising BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof, including heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, including a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof including in adoptive cell therapy.

Chimeric antigen receptors targeted to IL-13Ra2 are described. The targeting domain is a IL13 variant having increased specificity for IL-13Ra2 relative to IL-13Ra1.

The present invention belongs to the technical field of gene therapy. Provided are a chimeric antigen receptor nanocomposite and a preparation method therefor and the use thereof in the preparation of an anti-aging drug. The provided chimeric antigen receptor nanocomposite comprises a chimeric antigen receptor DNA plasmid specifically recognizing senescent cells, a polymer coupled with a signal peptide, a free polymer and an antibody polymer targeting T cells, wherein the chimeric antigen receptor DNA plasmid, the polymer coupled with a signal peptide, the free polymer and the antibody polymer targeting T cells are sequentially mixed and incubated to form the chimeric antigen receptor nanocomposite. The chimeric antigen receptor nanocomposite can rapidly generate senescent cell-marked chimeric antigen T cells in vivo. The engineered T cells have the ability to specifically eliminate senescent cells in vivo, and can rapidly and durably eliminate senescent cells in vivo, which is irreplaceable and has wide application prospects.

Provided is a chimeric antigen receptor targeting GCC, comprising: an scFv that specifically recognizes GCC, a CD8 hinge region or a CD28 hinge region, a CD8 transmembrane region or a CD28 transmembrane region, a CD28 co-stimulatory signal domain or a 4-1BB co-stimulatory signal domain, and a CD3ζ signal domain; the scFv that specifically recognizes GCC comprises a heavy chain variable region VH and a light chain variable region VL, the VH comprising an HC CDR1 having the amino acid sequence shown in SEQ ID NO: 1, an HC CDR2 having the amino acid sequence shown in SEQ ID NO: 2, and an HC CDR3 having the amino acid sequence shown in SEQ ID NO: 3, and the VL comprising an LC CDR1 having the amino acid sequence shown in SEQ ID NO: 4, an LC CDR2 having the amino acid sequence shown in SEQ ID NO: 5, and an LC CDR3 having the amino acid sequence shown in SEQ ID NO: 6.

The invention relates to the technical field of biomedicine, in particular to a fusion protein combining a double-target chimeric antigen receptor with PD-1 and IL-21, and an extracellular domain of the double-target chimeric antigen receptor sequentially comprises any one of the following components from an N terminal to a C terminal: CIgG scFv-MSLN scFv, CIgG scFv-CLDN18.2 scFv, CIgG scFv-MSLN scFv and CIgG scFv-CLDN18.2 scFv; wherein '-' is a connecting peptide; the cell further comprises a hinge region, a transmembrane region and an intracellular signal transduction region; pD-1 scFv and IL-21 are further fused at the N end of the intracellular signal transduction region. According to the invention, two chimeric antigen receptors of double-target combined PD-1 and IL21 fusion proteins are constructed, and through a synergistic anti-tumor strategy, CAR-T cell functions are enhanced, tumor microenvironment (TME) inhibition is overcome, T cell durability is improved, and synergy is realized.

Provided herein are novel Glypican 3 (GPC3) antibodies or antigen binding fragments and GPC3 / CD3 bispecific antibodies. The present application also provides chimeric antigen receptors comprising the antibodies or antigen-binding fragments, related CAR-T cells, and preparation methods and uses of the same. The present application further provides pharmaceutical compositions comprising GPC3 antibodies or antigen binding fragments, related GPC3 / CD3 bispecific antibodies, related GPC3 CAR or CAR-T cells, and methods of treating cancer in a subject in need thereof by administering the Glypican 3 (GPC3) antibodies or antigen binding fragments, the bispecific antibodies, the chimeric antigen receptors, the CAR-T cells, or the pharmaceutical compositions. The cancers treated in accordance with the application include Glypican-3-positive cancers.

The application provides an application of a FAP-targeted CAR-T cell in preparation of a drug for treating cardiac fibrosis in a chronic phase of myocarditis. It is found in the application that FAP-specific CAR-T cells can effectively target cells expressing mouse FAP proteins, and the CAR-T cells can effectively eliminate cells expressing mouse FAP proteins after being activated, the chimeric antigen receptor T cells effectively reduce cardiac fibrosis in a chronic phase of myocarditis in mice, and restore the function after inflammatory injury. The application develops a CAR-T therapy for myocardial fibrosis caused by a chronic phase of myocarditis, and the chimeric antigen receptor T cells expressing a targeted fibroblast activation protein can recognize activated myocardial fibroblasts, and significantly reduce cardiac fibrosis after inflammatory injury and restore the function.

Provided are expression constructs encoding chimeric antigen receptor and DAP10 recombinant polypeptide, engineered immune cells, and methods of use thereof. Further provided are activation and expansion of cells for therapeutic uses, especially for chimeric antigen receptor-based immune cell immunotherapy.

The present invention provides a chimeric antigen receptor (CAR) that recognizes CSPG4 as well as methods of use in the treatment of diseases and disorders.

Disclosed are VHH chimeric antigen receptors (VCARs), VCAR transposons encoding VCARs of the disclosure, cells modified to express VCARs of the disclosure, as well as methods of making and methods of using the same for adoptive cell therapy.

The present disclosure provides a population of CD4IL-10 / CAR cells (autologous or allogeneic single-donor and allogeneic polydonor) generated by genetically modifying CD4+ Tcells to express IL-10 and a chimeric antigen receptor. Further provided are methods of generating the CD4IL-10 / CAR cells and methods of using the CD4IL-10 / CAR cells for immune tolerization, treating GvHD, cell and organ transplantation, cancer, and autoimmune and inflammatory disorders.

The invention relates to the field of biomedical treatment, and particularly discloses application of CD146 in diagnosis and treatment of rhabdomyosarcoma, and the CD146 is specifically and highly expressed in tumor tissues of the rhabdomyosarcoma. The invention provides application of a biomarker for diagnosing rhabdomyosarcoma or / and a detection reagent thereof in preparation of a product for diagnosing rhabdomyosarcoma. Meanwhile, experiments prove that the CD146-targeted chimeric antigen receptor T cell has a relatively strong tumor cell killing effect and can effectively remove CD146 positive tumor cells. The CD146 biomarker provided by the invention provides a new target and theoretical basis for early diagnosis and individualized treatment of rhabdomyosarcoma, and has important clinical application value.

The invention provides an antibody for specifically targeting GPRC5D, an application of the antibody, and a single-domain antibody F08 for specifically targeting GPRC5D, wherein the binding activity and the reaction specificity of the single-domain antibody F08 for the GPRC5D are relatively high. The invention also provides nucleic acid molecules encoding the single domain antibodies, vectors and recombinant host cells, as well as methods of producing the single domain antibodies and antibody derivatives. The single-domain antibody provided by the invention can be used for constructing a chimeric antigen receptor T cell, and the chimeric antigen receptor T cell has stronger killing power on a target cell.

The invention provides methods and compositions for use in treating cancer, which advantageously may be achieved by targeting of the tumor microenvironment.

The invention provides a preparation method of a cell for expressing a chimeric antigen receptor. The preparation method comprises the following steps: (1) enabling the cell to be in contact with an activating agent for activation; (2) contacting the cell with a nucleic acid molecule for coding the CAR, the nucleic acid molecule for coding the CAR being on a non-viral vector, and obtaining the cell containing the nucleic acid molecule; and (3) harvesting cells. Wherein the step (3) is not later than 72 hours after the step (1) is started. Compared with cells prepared by other similar methods, the cells in the step (3) show a higher CAR positive rate, a higher proportion of undifferentiated cell phenotypes, a lower proportion of depleted cells and a stronger amplification ability.

Embodiments provided herein include methods and compositions comprising anti-dinitrophenol chimeric antigen receptors (CARs). Some embodiments include nucleic acids encoding such CARs, polypeptides encoded by such nucleic acids, cells comprising such nucleic acids or polypeptides, and methods utilizing such cells. Some embodiments also include the use of dinitrophenol (DNP) and derivatives thereof.

Provided herein are particles comprising polynucleotide constructs for generating cells expressing anti-CD22 chimeric antigen receptor, as well as vectors, such as lentiviral vectors, comprising same, cells comprising same, and methods of using same. Some embodiments include a surface-engineered lentiviral vector. In some embodiments, the lentiviral vector further encodes a synthetic receptor protein.