1633 results about "CAR - Chimeric antigen receptor" patented technology

The invention provides compositions and methods for treating diseases such as cancer. The invention also relates to a method of administering a therapy comprising a chimeric antigen receptor, an IL-15R molecule and an IL-15 molecule.

The invention provides a method of treating an adult subject having a hematological cancer, comprising administering to the subject selected dosage regimens comprising a plurality of immune effector cells expressing a CAR molecule.

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.

Disclosed are compositions and methods for preventing graft versus host disease (GVHD) in subjects receiving donor cells. In particular, chimeric antigen receptor (CAR) polypeptides are disclosed that can be used with adoptive cell transfer suppress alloreactive donor cells. Also disclosed are immune effector cells, such as T cells or Natural Killer (NK) cells, that are engineered to express these CARs. Therefore, also disclosed are methods of suppressing alloreactive donor cells in a subject receiving transplant donor cells that involves adoptive transfer of the disclosed immune effector cells engineered to express the disclosed CARs.

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 present disclosure provides bispecific chimeric antigen receptors that target BCMA and CD19. The CAR may comprise an scFv targeting BCMA and an scFv targeting CD19, a hinge region, a transmembrane domain, a co-stimulatory region, and a cytoplasm signaling domain. Chimeric antigen receptors can be used to treat autoimmune disorders or cancer.

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 provides immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions and methods thereof.

Aspects described herein pertain to engineered chimeric antigen receptors (CARs) and compositions thereof having specificity and affinity for fluorescein containing ligands presented on the surface of tumor cells. Also provided herein are compositions including CARs further comprising a spacer arm and methods of making and using these compositions.

Provided herein are methods and compositions for treating a subject having an autoimmune disorder, such as multiple sclerosis, autoimmune encephalitis, Sjogren's syndrome, kidney transplantation, IgG4-related disease, ANCA-associated vasculitis, chronic inflammatory demyelinating polyradiculoneuropathy, neuromyelitis optica spectrum disorder, and idiopathic inflammatory myopathy (e.g., antisynthetase syndrome, dermatomyositis, immune-mediated necrotizing myopathy, or polymyositis), using T cells engineered with a chimeric antigen receptor that binds CD19.

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 present disclosure provides chimeric antigen receptors, compostions, and methods thereof. In one embodiment the present disclosure provides a method of treating autoimmune diseases, asthma, and preventing or mediating organ rejection in a subject.

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 invention relates to immune cells engineered to express chimeric antigen receptors (CARs) that specifically bind to fibroblast activating proteins (FAPs) for use in the treatment of skeletal muscle fibrosis in muscular dystrophy.

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 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.

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.

Chimeric antigen receptors that include an antigen recognition domain; a spacer domain derived from a modified immunoglobulin Fc region having one or more mutations in its CH2 region resulting in impaired binding to an FcR; and an intracellular signaling domain.

The invention relates to methods for identifying unresponsive T cells and unresponsive chimeric antigen receptor-bearing T cells (CAR-T cells), methods of rejuvenation thereof and methods for improving CAR-T cell therapies.

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.

Disclosed herein are antibodies or antigen-binding fragments thereof that specifically bind to human CD19. Chimeric antigen receptors and chimeric antigen receptor transgenes comprising an antigen binding domain that specifically binds to human CD19 are also disclosed. Also described herein are immune cells, viral vectors, and other compositions containing the antibodies, the antigen binding fragments, the chimeric antigen receptors, and / or the chimeric antigen receptor transgenes.

The invention relates to the field of biological medicines, in particular to a chimeric cytokine activated receptor for activating lymphocytes by using soluble immunosuppressive molecules and application of the chimeric cytokine activated receptor in tumor treatment. The chimeric cytokine activation receptor and a chimeric antigen receptor for recognizing tumor antigens are connected in parallel to form a co-expressed polycistron structure. Wherein the chimeric cytokine activation receptor comprises an scFv structural domain, a transmembrane structural domain and a cytokine chimeric activation structural domain which specifically recognize and bind soluble immunosuppressive molecules. The CAR-NK cell can specifically recognize soluble inhibitory factors in the tumor microenvironment and improve the in-vivo and in-vitro anti-tumor efficacy of the CAR-NK cell, and can be used for treating solid malignant tumors.

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 for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

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.

Disclosed are compositions and methods for targeted treatment of cancer. The present disclosure provides chimeric antigen receptors and cells expressing such chimeric antigen receptors. In certain embodiments, engineered cells expressing the chimeric antigen receptors are specific for a low density cancer antigen or peptide in groove antigen.

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.