247 results about "Car t cells" patented technology

The present invention relates to T lymphocytes targeting CLD18A2 and a preparation method and application thereof. The inventors have successfully found a target gene CLD18A2 suitable for developing CAR T cells from a number of tumor-related genes for the first time, and successfully prepared CAR T cells targeting CLD18A2, thereby providing a new treatment method for pancreatic cancer, gastric cancer and other tumors.

The invention discloses application of kaempferol in promotion of gene editing, and belongs to the field of biological medicine. The application specifically comprises kaempferol as an accelerant for CRISPR (clustered regularly interspaced short palindromic repeats) gene editing and application of kaempferol in preparation of non-viral site-specific integrated CAR T cells. The invention finds that the kaempferol can significantly increase the CRISPR gene editing efficiency, and cell experiments find that the kaempferol has a significant promotion effect on the positive rate of CAR T cells after electrotransfection, and the tumor killing function of the T cells is greatly improved.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells wherein the CAR T cells comprise a CAR and the CAR comprises an E2 anti-fluorescein antibody fragment, and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

This document provides methods and materials involved in treating cancer. For example, methods and materials for modulating (e.g., increasing or decreasing) an interleukin-1 (IL-1) signaling pathway (e.g., an IL-1βsignaling pathway) during an adoptive cell therapy (e.g., a chimeric antigen receptor (CAR) T cell therapy) are provided. In some cases, one or more inhibitors of an interleukin-1 receptor antagonist (IL-1RA) polypeptide can be used to increasing IL-1 signaling (e.g., to reduce immunosuppression of the administered cells). In some cases, CAR T cells having a reduced level of an interleukin 1 receptor, type I (IL-1R1) polypeptide can have decreased IL-1 signaling (e.g., to reduce T cell toxicity associated with the administered cells).

The invention discloses a CAR donor plasmid, a T cell as well as a preparation method and application of the CAR donor plasmid and the T cell, and belongs to the field of genetic engineering and immune cell therapy. An RNP compound and donor plasmid DNA are transferred into a T cell through electroporation, and a CAR expression unit is integrated into a T cell genome at a fixed point to prepare the CAR T cell. The donor plasmid DNA comprises a plasmid skeleton, a homologous arm sequence, an EF1 alpha core promoter, a CAR expression element and an SV40 poly A termination signal. The number of base pairs of the plasmid is 4544 bp, the toxicity of the plasmid to T cells after electroporation can be effectively reduced, and the T cell viability and the CAR integration efficiency are improved. Compared with dsDNA and ssDNA, the plasmid DNA is convenient to prepare and low in cost; therefore, the plasmid is taken as the donor template DNA, and the CRISPR / Cas9 technology is combined, so that the use of a virus vector can be avoided to improve the safety of the CAR T cell, and the production cost of the preparation of the CAR T cell can be effectively reduced.

The invention provides improved anti-BCMA CAR T cell compositions for adoptive T cell therapy for relapsed / refractory multiple myeloma.

The present disclosure relates generally to methods for generating a pre-effector gene signature for determining the C cytotoxic effector potential of a preparation of chimeric antigen receptor (CAR) T cells comprising measuring single-cell gene expression data and endogenous T cell receptor (TCR) sequencing data of the preparation of CAR T cells. The present invention relates also to methods for determining the cytotoxic effector potential of a preparation of CAR T cells or a subset of CAR T cells therefrom as well as methods for treating a cancer in a subject in need thereof by administering a preparation of CAR T cells determined to have a cytotoxic effector potential.

Relates generally to engineered cells, e. g. CAR T cells expressing trimeric complexes. Further provides fusion polypeptides which participate in the formation of the trimeric complexes.

The present disclosure relates to methods of treating a patient with a cancer by administering to the patient a composition comprising CAR T cells and administering to the patient a small molecule linked to a targeting moiety by a linker. The disclosure also relates to compositions for use in such methods.

The invention provides improved anti-BCMA CAR T cell compositions for adoptive T cell therapy for relapsed / refractory multiple myeloma.

An oncolytic poxvirus encoding a truncated human CD19 is used in conjunction with a chimeric antigen receptor to treat solid tumors.

Nanoparticles for engineering cells to express target antigens and methods of treating / preventing cancer or solid tumors using the same.

The present disclosure provides methods of rapidly manufacturing genetically modified immune effector cells, such as T cells. The method allows fast (llt; 1 day) to produce genetically modified immune effector cells, such as CAR T cells.

Provided herein are anti-idiotypic antibodies that specifically recognize anti-CD70 antibody portions, particularly anti-CD70 antibody portions present in recombinant receptors, including chimeric antigen receptors (CARs). The present disclosure further relates to the use of anti-idiotypic antibodies to specifically identify and / or select cells expressing such recombinant receptors, such as anti-CD70 CAR T cells. The present disclosure further relates to the use of anti-idiotypic antibodies to specifically activate such cells.

The present disclosure relates to mesothelin chimeric antigen receptors (CARs), T cell engaging molecules (TEAMs), anti-mesothelin-CAR T cells optionally comprising TEAMs, and methods of use thereof.

The present invention discloses a modified chimeric antigen receptor T cell, its preparation method, and its use. The present invention prepares cells, such as chimeric antigen receptor T cells, modified with a hydrophobic two-dimensional sheet material. Compared to simple chimeric antigen receptor T cells, these cells can bind to more leukemia cells, enhancing their recognition and killing abilities. Furthermore, the nanomaterial's high specific surface area provides space for drug loading, enabling the combination of CAR T cells with other therapies.

The application discloses an application of kaempferol in promoting gene editing and belongs to the field of biological medicines. The application specifically comprises kaempferol as a promoter of CRISPR gene editing and the application of kaempferol in preparing non-virus site-specific integration CAR T cells. It is found that kaempferol can significantly increase the efficiency of CRISPR gene editing, and it is found through cell experiments that kaempferol has a significant promoting effect on the positive rate of CAR T cells after electrotransformation, and greatly improves the tumor killing function of T cells.

Systems and methods are disclosed for predicting whether a patient-specific CAR T drug product for a target patient would undergo growth termination. An example method includes: receiving quantitative data for a set of growth termination parameters; generating an input feature vector comprising the quantitative data for the set of growth termination parameters; and applying, into a trained machine learning model, the input feature vector to generate an output feature vector predicting whether the patient-specific CAR T drug product would undergo growth termination.

The present disclosure relates generally to methods of making a population of trispecific CAR-expressing immune cells that provide several improvements over existing manufacturing methods, thereby enabling production of a robust supply of clinically useful CAR T-cell therapies.

The present disclosure provides a universal and multifunctional platform for transcriptome modulation that utilizes RNA-guided RNA targeting activity that binds to a VI-D type CRISPR effector with RNA-guided RNA endonuclease activity that expresses a guide array of a plurality of guide RNAs. The system can be used for quantitative, reversible and large-scale multiplex gene knock-down in primary human T cells, and multiplex inhibition of consumption related genes in T cells. The system can be used for enhancing the anti-tumor activity of dysfunctional CAR T cells.

The invention discloses application of amifostine to improvement of fixed-point insertion efficiency of a genome, and belongs to the field of biological medicine. Specifically, amifostine provided by the invention can significantly improve the CRISPR gene editing efficiency, and especially can be used for preparing non-viral site-specific integrated CAR T cells. Through cell experiments, it is found that amifostine has a remarkable promoting effect on the positive rate of CAR T cells after electrotransfection, and the tumor killing function of the T cells is greatly improved.

The invention relates to a CLD18A2-targeted T lymphocyte as well as a preparation method and application thereof. The inventor successfully finds a target gene CLD18A2 suitable for developing CAR T cells from a plurality of tumor related genes for the first time, and successfully prepares CLD18A2-targeted CAR T cells, so that a brand new treatment means is provided for pancreatic cancer, gastric cancer and other tumors.

The present disclosure provides methods of treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder by administering hypoimmune allogenic CD22-directed CAR T cells. Also disclosed are pharmaceutical compositions comprising hypoimmune allogenic CD22-directed CAR T cells, for use in treating a subject having or suspected of having a B cell malignancy or a B cell mediated disorder.

Methods and compositions are provided for reversibly localizing proteins to the exterior part of the cell surface. Essentially, the protein must comprise, in addition to a transmembrane domain, also a hormone receptor like the estrogen receptor alpha or the progesterone receptor. Compositions provided herein can include nucleic acids that encode polypeptides of interest and the ligand binding domain (LBD) of a nuclear hormone receptor. Medical applications are provided, including controlling the toxicity of CAR T cells.

To provide a method of manufacturing chimeric antigen receptor-expressing T cells (CAR T cells) from peripheral blood mononuclear cells (PBMCs) from a subject from which a blood sample is obtained.SOLUTION: The manufacturing method comprises a step (a) of obtaining the PBMCs from the blood sample; a step (b) of isolating the PBMCs obtained from the blood sample, by using a membrane filtration system and ammonium chloride-potassium buffer; a step (c) of washing the PBMCs via centrifugation; a step (d) of optionally cryopreserving the PBMCs; a step (e) of optionally thawing the PBMCs cryopreserved in the step (d); a step (f) of washing the PBMCs using a membrane filtration system; a step (g) of manufacturing the CAR T cells from the PBMCs from the step (f); and a step (h) of washing the CAR T cells from the step (g) by using a membrane filtration system.SELECTED DRAWING: None

Disclosed herein are methods of sorting antigen specific T cells without activating; methods that employ said sorting methods to engineer chimeric antigen receptor (CAR) T cells; methods that employ said sorting methods in adoptive cell therapies and kits comprising the components for performing the disclosed methods.

The present disclosure relates to methods and compositions for the treatment of a mammalian subject suffering from lupus the method comprising, administering to said subject a therapeutically effective amount of an orthogonal CAR-T cell directed against a B-cell antigen in combination with an engineered orthogonal IL2 ligand that selectively activates orthogonal CAR T cell expressing an engineered orthogonal CD122 receptor. In some embodiments, the lupus is systemic lupus erythramatosis (SLE). In some embodiments, the lupus is lupus nephritis. In some embodiments the subject suffering from lupus is also suffering from cytopenia. In some embodiments the methods are practiced in the absence of prior lymphodepletion of the subject.

Chimeric antigen receptor (CAR) linking molecules and protein entities and dimers comprising an extracellular domain of an antigen present on a cancer cell and a first immune cell effector domain are disclosed, as well as their use in co-treatment of cancer with CAR immune cells.

The disclosure provides constructs that permit hypoxia-controlled expression to be selectively active in tumors and tumor microenvironments, thereby reducing off target effects of expressed therapeutic genes, such as CAR T cells.