172 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 present invention provides composition kits and methods for treating cancer in a human by immunotherapy using successive doses of CAR-T cells with no or reduced anamnestic immune reaction in one individual (P).

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.

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 present invention encompasses methods of cancer immunotherapy, and particularly methods of allogeneic cellular immunotherapy, used in populations of subjects having cancer who previously received an autologous cell therapy, had a response, and subsequently relapsed.

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 discloses an immune cell for enhancing cell immunotherapy and expressing non-secreting IL-10, a preparation method and application thereof, and accidentally finds that compared with secreting IL-10, the non-secreting IL-10 can obviously relieve mitochondrial dysfunction of CAR cells, and compared with the secreting IL-10, the non-secreting IL-10 can obviously relieve the mitochondrial dysfunction of the CAR cells when the non-secreting IL-10 is stimulated by target cells, so that the non-secreting IL-10 can obviously relieve the mitochondrial dysfunction of the CAR cells. The non-secreting IL-10 can effectively improve the motility rate of CAR cells and reduce the occurrence of CAR apoptosis. On the basis, non-secreting IL-10 is expressed in the CAR cells, so that the main toxic and side effects of a CAR cell therapy are effectively relieved, meanwhile, the tumor killing ability of the CAR cells is remarkably improved by protecting the mitochondrial function of the CAR cells, improving the motility rate of the CAR cells and reducing the occurrence of CAR cell apoptosis, and the toxicity reducing and synergistic effects of the CAR cells are achieved.

The present invention provides nucleic acids, vectors, host cells, methods and compositions to confer and / or augment immune responses mediated by cellular immunotherapy, such as by adoptively transferring CD8+ central memory T cells or combinations of central memory T cells with CD4+ T cells that are genetically modified to express a chimeric receptor under the control of an inducible promoter. In some alternatives the genetically modified host cell comprises a nucleic acid comprising a polynucleotide coding for a chimeric antigen receptor comprising a ligand binding domain, a polynucleotide comprising a spacer region, a polynucleotide comprising a transmembrane domain, and a polynucleotide comprising an intracellular signaling domain under the control of a drug inducible promoter. Controlling the expression of the chimeric receptor provides for the ability to turn expression on and off depending on the status of the patient. Pharmaceutical formulations produced by the method, and methods of using the same, are also described.

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 invention discloses a double-epitope CAR targeting CLL1, a double-epitope CAR-T cell and application of the double-epitope CAR and the double-epitope CAR-T cell, and belongs to the technical field of cellular immunotherapy. The technical problem to be solved by the invention is how to improve the killing activity of the CLL1-targeted chimeric antigen recipient cell on CLL1-positive tumor cells and / or the immunosuppression effect of resisting a tumor microenvironment. The invention specifically discloses a chimeric antigen receptor with an amino acid sequence as shown in SEQ ID No.1, a fusion protein with an amino acid sequence as shown in SEQ ID No.3, and a double-epitope CAR-T cell constructed by using the chimeric antigen receptor and the fusion protein. The double-epitope CAR-T cell disclosed by the invention can well secrete T cell specific effector molecules IFN-gamma, effectively and specifically kill CLL1 + target cells, and has good in-vivo tumor killing activity. The antibody can be used for immunotherapy of CLL1 target related diseases, and has a wide clinical application prospect.

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 relates to the field of cancer. In particular, it relates to the field of immune system directed approaches for tumor treatment, reduction and control. Some aspects of the invention relate to the identification of tumor specific neoantigens, such as those resulting from frameshift mutations, DNA rearrangements, or splicing mutations. Such neoantigens are useful for developing tumor treatments, such as vaccines or cellular immunotherapies and other means of stimulating a neoantigen specific immune response against a tumor in individuals.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors as well as genetically edited or otherwise engineered to alter the effectiveness with which another immune cell can target and induce cytotoxic effects on the engineered cells. In several embodiments, the methods and compositions disclosed herein reduce fratricide within a therapeutic cell population, which in some instances comprises mixture of immune cell types. Additionally, the methods and compositions disclosed herein enhance one or more aspects of the efficacy of the immune cells in cellular immunotherapy including cytotoxicity and / or persistence, as well as reduced graft versus host or host versus graft effects.

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.