129 results about "Cellular immunotherapy" patented technology

The invention relates to the technical field of cellular immunotherapy, in particular to application of efonidipine in preparation of a dendritic cell immunologic adjuvant. The invention provides an application of efonidipine in preparation of a dendritic cell immunologic adjuvant. It is found that efonidipine can promote maturation, migration and antigen presentation functions of DCs, and the homing ability of DCs and CD8 + T cell activation are remarkably improved. The activation aspect of efonidipine on DCs comprises improvement of expression of maturation indexes CD80, CD40 and CD86, expression of a migration index CCR7, activation of CD8 + T cells by antigen presentation and the like. The efonidipine used in the invention is a drug approved by FDA for clinical treatment of cardiovascular diseases, the application of the efonidipine in immunotherapy is found, new use of old drugs is realized, and the efonidipine has great economic value.

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.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture, through the repeated co-culturing of NK cells with feeder cells and the selective use of stimulatory interleukins. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, which results in a highly expanded and highly cytotoxic population of cells, for use in, for example allogeneic cellular immunotherapy.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are gene edited (e.g., using Crispr / Cas) to modulate, reduce, or otherwise eliminate expression of one or more endogenous genes. In several embodiments, the edited cells are engineered to express chimeric antigen receptors that target tumor antigens (e.g., CD19, ligands of the NKG2D receptor, CD70, and / or BCMA, etc.). In several embodiments, the editing enhances one or more aspects of immune cell efficacy in cellular immunotherapy, including cytotoxicity (e.g., ADCC) and / or persistence.

The disclosure provides methods of treating a malignancy comprising administering an effective dose of an immune cell therapy (e.g., a chimeric antigen receptor genetically modified T cell immunotherapy) and methods for manufacturing such immunotherapy. Some aspects of the disclosure relate to methods of determining objective response of a patient to an immune cell immunotherapy based on the levels of patient and product attributes prior to and after administration of the immunotherapy to the patient.

The invention provides a preparation method and application of CAR-T cells for overexpressing C1QBP, and relates to the field of cell engineering. According to the CAR-T cell overexpressing the C1QBP, the energy metabolism of the cell is optimized by improving the oxidative phosphorylation of mitochondria, the formation of memory-like T cells is promoted, and the anti-tumor activity and long-term durability of the CAR-T cell are enhanced. The cells can survive in a tumor microenvironment for a long time, and the anti-tumor effect of the cells is more durable than that of traditional CAR-T cells. Therefore, a new direction is provided for research and development of cellular immunotherapy.

The invention belongs to the technical field of autoimmune skin disease immunotherapy, and provides a three-target novel chimeric autoantibody receptor structure which comprises three chimeric receptors through two connecting peptides, specifically, a first chimeric autoantibody receptor comprises a Dsg1 extracellular structural domain; the second chimeric autoantibody receptor comprises a Dsg3 extracellular structural domain; the third chimeric antigen receptor comprises an extracellular domain capable of targeting a B cell associated antigen; wherein the Dsg1 extracellular structural domain is an extracellular structural domain of desmosome core glycoprotein 1; the Dsg3 extracellular structural domain is the extracellular structural domain of desmosome core glycoprotein 3. In-vitro experiments and animal experiments verify that the novel three-target CAAR-T cells can significantly increase the release of cytokines, enhance the targeted killing activity of the cytokines, and show better multiplication capacity; a novel cellular immunotherapy technology is provided for treating autoimmune skin diseases, and the application of CAAR-T in the field of autoimmune disease treatment can be expanded.

The invention belongs to the technical field of cellular immunotherapy, and particularly relates to a targeted MSLN chimeric antigen receptor macrophage, a preparation method thereof and application of the targeted MSLN chimeric antigen receptor macrophage to treatment of MSLN positive tumors. According to the present invention, the chimeric antigen receptor modified engineering immune cell specifically targeting MSLN is prepared by using the chimeric antigen receptor modified macrophage technology, the preparation method has simple steps, and the obtained novel engineering immune cell can specifically recognize tumor cells, can more effectively target and attack the tumor cells, has a high tumor killing rate, and can be used for preparing the MSLN-targeted engineering immune cell. The compound can be used for preparing anti-tumor products, especially for preparing drugs for treating MSLN positive tumors, especially for preparing drugs for treating ovarian cancer malignant pleural mesothelioma, pancreatic cancer and part of lung cancer, and has good industrial application prospects.

The disclosure provides methods of treating a malignancy comprising administering an effective dose of a chimeric antigen receptor genetically modified T cell immunotherapy and methods for manufacturing such immunotherapy. Some aspects of the disclosure relate to methods of determining objective response of a patient to a T cell immunotherapy based on the levels of attributes prior to and after administration of the immunotherapy to the patient.

This document provides methods and materials involved in treating a mammal (e.g., a human) having cancer (e.g., a cancer including one or more solid tumors). For example, methods and materials provided herein can be used to sensitize a cancer to immune checkpoint blockade (ICB) (e.g., administration of one or more immune checkpoint inhibitors). For example, a mammal having cancer can be administered (a) one or more inhibitors of a NOS2 polypeptide and (b) one or more inhibitors of a COX2 polypeptide to sensitize the cancer to ICB and, optionally, can also be administered one or more immune checkpoint inhibitors to treat the cancer. In another example, a mammal having cancer can be administered (a) one or more inhibitors of a NOS2 polypeptide and (b) one or more inhibitors of a COX2 to enhance cellular immunotherapy and, optionally, can also be administered one or more cellular immunotherapies to treat the cancer.

Provided are methods for treating a subject of a solid tumor expressing GPC3 comprising administering to the subject an anti-GPC3 chimeric antigen receptor immunoresponsive cell wherein the administering is performed after or concurrently with subjecting the subject to a lymphopenia treatment. A kit for use in the method is also provided.

Provided for herein in several embodiments are anti-BCMA binding moieties. These anti-BCMA binding moieties may be used in BCMA-directed chimeric antigen receptors (CARs). Also disclosed herein are immune cell-based compositions comprising the anti-BCMA binding moieties and BCMA-directed CARs. In several embodiments, the immune-cell based compositions also target an additional tumor marker and / or an additional epitope of BCMA. In several embodiments, the BCMA-directed CAR is expressed in a Natural Killer cell. In several embodiments, combinations of BCMA-CAR-expressing NK cells are administered in conjunction with, for example CAR-expressing NK cells and / or CAR-expressing T cells that are directed to an additional cancer marker and / or an additional epitope of BCMA. Also provided for herein are methods and uses of the chimeric antigen receptors in immunotherapy.

The present invention pertains to the field of cellular immunotherapy. More precisely, it is directed to therapeutic interventions against cancer, immunodeficiency, infectious diseases, and autoimmune conditions utilizing human memory-like cytotoxic lymphocytes, including T cells, Natural Killer (NK) cells, Natural Killer T (NKT) cells, monocytes and other relevant cell types. Disclosed are methods for the isolation and induction of these cells into a memory-like state, which can find application in therapeutic contexts as well as in non-therapeutic contexts, such as in research endeavors.

A nanoparticle and a preparation method therefor, the nanoparticle including an amphiphilic peptide, which forms a micelle structure through self-assembly, and a target peptide (preferably, a water-soluble antigen peptide), which electrically binds to the surface of the amphiphilic peptide. The target peptide electrically binds to the surface of the amphiphilic peptide micelle structure and becomes particulated, and thus can be effectively presented to an antigen-presenting cell, and the weight ratio of the amphiphilic peptide and the target peptide is controlled so that the size of nanoparticles is controlled and endocytosis thereof is carried out, and thus immunity by means of cytotoxic T cells can be induced. Nanoparticles exhibit use only an epitope of a more accurate region so as to be effective as a vaccine, and thus have minimal side effects. Therefore, excellent antigen-specific antibody and cell immunotherapy effects are exhibited, and thus can be used in various fields such as vaccine production.

The invention specifically discloses a FAP-targeted chimeric antigen receptor as well as a preparation method and application thereof, and relates to the technical field of cellular immunotherapy. The invention provides a chimeric antigen receptor, the chimeric antigen receptor comprises an extracellular structural domain and a growth factor, the extracellular structural domain comprises an FAP antigen binding structural domain specifically bound with FAP, and the growth factor is FGF; and an immune cell expressing the modified chimeric antigen receptor, such as CART, which has an efficient killing ability to a target cell overexpressing FAP; and massive regeneration of hepatic cells is promoted after hepatic fibrosis is treated. The invention provides a theoretical basis and an experimental basis for developing a new treatment strategy, and has good clinical transformation and clinical application prospects.

A method for treating a tumor, characterized by administering to an individual having a tumor immune effector cells expressing a receptor recognizing a tumor antigen and gemcitabine. A kit for treating a tumor, characterized by comprising: 1) immune effector cells expressing a receptor recognizing a tumor antigen; 2) gemcitabine; 3) a container for containing the above 1) and 2); and 4) a written notice for treating a tumor using the kit.

The invention relates to the technical field of cellular immunotherapy, in particular to an antigen epitope peptide of a CD40 ligand, an antibody and application. The CD40LG target is mainly expressed by CD4 + T cells, so that self-killing is greatly reduced. In addition, as a novel target, the CD40LG can effectively improve tumor immune escape. The antibody provided by the invention can specifically recognize CD40LG, and has good affinity. The compound can be used for constructing cells or ADC drugs for adoptive immunotherapy.

A method for treating a tumor, characterized by administering to an individual having a tumor immune effector cells expressing a receptor recognizing a tumor antigen and gemcitabine. A kit for treating a tumor, characterized by comprising: 1) immune effector cells expressing a receptor recognizing a tumor antigen; 2) gemcitabine; 3) a container for containing the above 1) and 2); and 4) a written notice for treating a tumor using the kit.

Provided are methods for treating a subject of a solid tumor expressing GPC3 comprising administering to the subject an anti-GPC3 chimeric antigen receptor immunoresponsive cell wherein the administering is performed after or concurrently with subjecting the subject to a lymphopenia treatment. A kit for use in the method is also provided.

The present application relates to the technical fields of biological medicine and cellular immunotherapy, and particularly relates to a signal conversion receptor targeting IL-10, an engineered macrophage and application thereof. The signal conversion receptor is composed of an extracellular domain and a transmembrane domain and an intracellular domain derived from TLR9, and the extracellular domain sequentially comprises a signal peptide, a HA tag and a specific binding domain of an IL-10 receptor alpha subunit from N-terminal to C-terminal. The present application further prepares an engineered macrophage SR CAR-M capable of specifically recognizing IL-10 and converting it into a TLR9 activation signal, which can induce macrophages to polarize to M1 type and has excellent phagocytosis and killing capacity for bladder cancer, breast cancer, lung cancer and melanoma cells, and can be used for preparing related tumor treatment drugs, overcoming the common problems of existing cell therapy, such as easy exhaustion, difficult infiltration and easy inhibition in solid tumors, and having significant clinical transformation potential.

The application belongs to the field of cell therapy process engineering, and discloses a CAR-NK cell high-yield culture method with dynamic process control. The method realizes the dynamic balance of nutrient supply and shear force in the culture system by introducing the strategy of combining culture stage regulation with one-time large-volume liquid replacement in a swing bioreactor. The method realizes online interception and rapid replacement of the culture medium in the high-density cell stage by using the built-in interception membrane of the reactor culture bag, thereby avoiding cell loss and nutrient depletion. Meanwhile, the method effectively maintains the CAR expression level and cell functional activity by cooperating with the optimized culture medium formula and the application of a transfection aid. The method has the advantages of simple operation and high repeatability, is suitable for various swing or closed reactor platforms, has good amplification performance and industrial application value, and can provide an efficient and stable technical scheme for the preclinical preparation and industrial production of CAR-NK cell immunotherapy.

The invention provides application of overexpressed CDCA5 in preparation of a medicine for enhancing the anti-tumor function of T cells, and relates to the technical field of cellular immunotherapy. According to the method for overexpressing the CDCA5, a CDCA5 overexpression agent is used, the CDCA5 overexpression agent is a carrier for overexpressing the CDCA5, and the carrier for overexpressing the CDCA5 is any one of lentivirus and retrovirus. The invention overcomes the defects of the prior art, verifies that the CAR-T overexpressing CDCA5 obviously enhances the anti-tumor function in vivo and in vitro, and provides a new technical direction for anti-tumor treatment.

The presently disclosed subject matter provides compositions and systems for cell-based immunotherapy. In certain non-limiting embodiments, the system comprises a membrane-bound polypeptide and at least one soluble polypeptide that is capable of dimerizing with the membrane-bound polypeptide.

This document provides methods and materials involved in treating a mammal (e.g., a human) having cancer (e.g., a cancer including one or more solid tumors). For example, methods and materials provided herein can be used to sensitize a cancer to immune checkpoint blockade (ICB) (e.g., administration of one or more immune checkpoint inhibitors). For example, a mammal having cancer can be administered (a) one or more inhibitors of a NOS2 polypeptide and (b) one or more inhibitors of a COX2 polypeptide to sensitize the cancer to ICB and, optionally, can also be administered one or more immune checkpoint inhibitors to treat the cancer. In another example, a mammal having cancer can be administered (a) one or more inhibitors of a NOS2 polypeptide and (b) one or more inhibitors of a COX2 to enhance cellular immunotherapy and, optionally, can also be administered one or more cellular immunotherapies to treat the cancer.

The present invention belongs to the technical fields of biomedicine and molecular biology, and particularly relates to a single-chain fragment variable (scFv) targeting human platelet-derived growth factor receptor (PDGFR)-β and use thereof in chimeric antigen receptor (CAR)-T cell immunotherapy. In the present invention, a scFv sequence targeting a human-derived PDGFRβ antigen is first obtained by immunizing a mouse, and then a second-generation CAR is constructed based on this, and additionally a CAR-T cell is obtained via lentivirus infection. The CAR-T cell can effectively kill a PDGFRβ antigen-positive 293T cell. The present invention provides a brand-new idea for eliminating PDGFRβ-positive cells to treat chronic kidney diseases, chronic liver diseases, cardiovascular diseases and various tumor diseases including various organ fibrosis, and has extremely attractive further development value and application prospects.

To provide engineered cells using the cytotoxic activated natural killer cell line as the basis to improve immunotherapies to cancer and tumors.SOLUTION: The present invention provides a recombinant modified natural killer (NK)-92 cell stably transfected with nucleic acids, wherein the recombinant modified NK-92 cells have American Type Culture Collection (ATCC) deposit number CRL-2407; the nucleic acid encodes an anti-cluster of differentiation 123 (CD123) chimeric antigen receptor (CAR), an Fc receptor, and a cytokine; and the recombinant modified cells express the anti-CD123 CAR and the Fc receptor on the cell surface of the recombinant cells.SELECTED DRAWING: Figure 16

Provided herein are methods and compositions for modifying the genome of human T cells.Furthermore, the compositions and methods described herein can be used to generate human T cells with altered specificity and functionality while limiting the side effects associated with T cell therapy.Provided herein are human T cells that heterologously express one or more polypeptides.In some embodiments, one or more polypeptides, for example, two or more polypeptides, are encoded by a nucleic acid construct that is inserted into the TCR locus of the cell. TIFF2025506185000058.tif91170

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are genetically edited, for example, using Crispr / Cas, to modulate, reduce or otherwise eliminate expression of one or more endogenous genes. In several embodiments, the edited cells are engineered to express a chimeric antigen receptor targeting a tumor antigen, for example CD19, ligands of the NKG2D receptor, CD70, and / or BCMA, among others. In several embodiments, the editing enhances one or more aspects of the efficacy of the immune cells in cellular immunotherapy including cytotoxicity (e.g., ADCC) and / or persistence.

The present disclosure relates to the fields of molecular biology, more specifically antigen-binding molecule technology. The present disclosure also relates to methods of medical treatment and prophylaxis, particularly cellular immunotherapy.

The invention relates to the technical field of cellular immunotherapy, in particular to application of drafenib mesylate in preparation of a dendritic cell (DCs) immunologic adjuvant. The invention provides an application of drafenib mesylate in preparation of a dendritic cell immunologic adjuvant. It is found that darfenib mesylate can promote the maturation and migration functions of DCs, and the migration ability of DCs is remarkably improved. The DCs activation aspect of the darfenib mesylate comprises improvement of expression of maturation indexes CD80, CD40 and CD86 and expression of a migration index CCR7. Darrafenib mesylate used in the invention is a chemotherapeutic drug approved by FDA for clinical treatment of patients with BRAF V600 mutation positive non-resectable or metastatic melanoma, the application of Darrafenib mesylate in immunotherapy is discovered, new use of old drugs is realized, and the Darrafenib mesylate has significant economic value.