87 results about "Cellular immunotherapy" patented technology

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.

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.

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.

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.

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.

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.

This invention provides a method for manipulating the CIITA gene to reduce or avoid immune rejection of CD4+ T cells in CAR-T cell immunotherapy. [Solution] The present invention provides a method for knocking out the CIITA gene by introducing a spacer sequence, a nucleic acid encoding the sgRNA, a vector containing the nucleic acid, and a Cas9 nuclease into cells, which specifically targets the CIITA gene.

The invention relates to the technical field of cellular immunotherapy, and discloses an application of a CD74 positive regulatory T cell in treatment of graft versus host disease, the CD74 positive regulatory T cell is composed of the following components in proportion: in a sorted and purified cell population, the proportion of regulatory T cells with CD4 + CD25 + CD127-phenotype is 85-95%, the proportion of regulatory T cells with CD25 + CD127-phenotype is 1-5%, and the proportion of regulatory T cells with CD24 + CD25 + CD127-phenotype is 1-5%. Wherein the CD74 high-expression subgroup accounts for 60-75% of the total amount of the regulatory T cell, the cell subgroup functional immune molecule combination comprises CTLA4, FOXP3, TIGIT and TNFRSF18, when the CD74 positive regulatory T cell is used for treating graft versus host disease, the CD74 positive regulatory T cell is firstly used for preventive infusion, single infusion is performed on the day of transplantation, the dosage is 5 * 10 < 5 > cells / receptor, and then the CD74 positive regulatory T cell is used for treating the graft versus host disease. The CD74 positive regulatory T cells are used for repeated therapeutic infusion when early aGVHD symptoms occur, graded treatment is carried out, pathological immune response is inhibited to the maximum extent, immune tolerance is promoted, the treatment is carried out once a week and 2-3 times in total, and the dosage of each time is 1 * 10 < 6 > cells / receptor.

The application discloses application of ostruthin in enhancing CAR-T cell anti-tumor function, belongs to the technical field of biological medicine, and the ostruthin can promote cell proliferation, inhibit cell exhaustion, promote the secretion of cytokines related to killing cancer cells, and further enhance the anti-tumor function of CAR-T cells in vivo and in vitro as a cell enhancer of CAR-T cells; experimental results show that when ostruthin is combined with CAR-T cells for anti-tumor treatment, compared with ostruthin or CAR-T cells alone, the combination of the two can significantly inhibit the growth of solid tumors. The application provides a new technical means for improving the tumor treatment effect of CAR-T cell immunotherapy.

The invention discloses a chimeric receptor with an anti-transplant rejection function and an engineering cell for expressing the chimeric receptor, and further relates to a method for resisting tumors and transplant immunological rejection, in particular to a method for resisting NK cell immunological rejection. The invention also relates to cell therapy.

The present disclosure provides a method for treating a tumor in a subject in need thereof, the method comprising administering to the subject an effective amount of a combination of a CLDN18.2 antagonist and a GUCY2C antagonist or an antagonist of CLDN18.2 and GUCY2C. The disclosure also provides multispecific chimeric antigen receptor constructs, combinations of chimeric antigen receptors, engineered immune cells, and methods of use thereof. The disclosure further relates to the activation and expansion of cells for therapeutic use, especially for chimeric antigen receptor-based T cell immunotherapy.

Provided herein are methods and compositions for modifying the genome of human T cells. Further, 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 therapies. Provided herein is a human T cell that heterologously expresses one or more polypeptides. In some embodiment, the one or more polypeptides, for example, two or more polypeptides, are encoded by a nucleic acid construct inserted into the TCR locus of the cell.

Embodiments of the present disclosure encompass compositions comprising immune effector cells, such as natural killer (NK) cells, wherein the cells comprise one or more exogenously provided interleukins (ILs), and optionally, the cells comprise one or more engineered receptors. In certain embodiments, the ILs are not IL-15, but are IL-12, IL-21, or both. The NK cells can be used to treat any type of cancer, including at least glioblastoma.

A cancer neoantigen-expressing cell membrane GRP94-targeting chimeric antigen receptor, comprising a signal peptide region, a cell membrane GRP94-targeting antigen binding domain, a hinge region, a transmembrane domain, and a signal transduction activation domain which are connected in sequence from the amino terminus to the carboxyl terminus, wherein the nucleotide sequence and amino acid sequence of the signal peptide region are as shown in SEQ ID No: 1 and SEQ ID No: 2 respectively; and the antigen binding domain is a portion of an antibody itself that targets cancer neoantigen-expressing cell membrane GRP94, or formed between portions of the antibody itself or between a portion thereof and an antibody region for another target. A novel chimeric antigen receptor (CAR)-engineered NK immune cell and a cancer drug can rapidly induce apoptosis in novel cancer cells having potentially cancer antigen-expressing cell membrane GRP94 protein, generate no toxic and side effects such as cytokine storms, and have off-the-shelf universal applicability, thereby providing a new choice for cell immunotherapy for cancers and also laying a foundation for accurate individualized treatment for cancer treatment.

The invention belongs to the technical field of cellular immunotherapy, and particularly relates to a targeted FAP chimeric antigen receptor macrophage as well as a preparation method and application thereof. According to the invention, FAP is taken as a target spot to design a CAR carrier of a specific targeted activated hepatic stellate cell, and a CAR-M cell for treating hepatic fibrosis is constructed. The macrophage expressing the chimeric antigen receptor has a remarkable killing effect on FAP positive cells, and a new thought is provided for clinical treatment of hepatic fibrosis, liver cirrhosis and liver cancer.

The present invention belongs to the technical field of cellular immunotherapy and relates to an intracellular domain of a chimeric antigen receptor and uses thereof in Chimeric Antigen Receptor T (CAR-T) cell therapy.

The invention discloses application of thiamine pyrophosphoric acid in enhancing the anti-tumor function of T cells and CAR-T cells, and belongs to the technical field of biomedicine.The thiamine pyrophosphoric acid serving as a cell enhancer of the T cells and the CAR-T cells can promote cell proliferation, inhibit cell depletion and promote cells to secrete cytokines related to killing cancer cells at the same time, and the anti-tumor function of the T cells and the CAR-T cells is enhanced. Further, the in-vivo and in-vitro anti-tumor functions of the T cells and the CAR-T cells can be enhanced; experimental results show that when the thiamine pyrophosphate is combined with the T cell or the CAR-T cell to carry out anti-tumor treatment, compared with independent use of the T cell or the CAR-T cell, the combined application of the thiamine pyrophosphate and the T cell or the CAR-T cell can obviously inhibit the growth of various solid tumors. The invention provides a new strategy for improving cell immunotherapy based on T cells or CAR-T cells.

The invention discloses a method for improving proliferation and activity of cytokine-induced killer cells, and belongs to the technical field of cellular immunity. According to the method, the human peripheral blood mononuclear cells are firstly cultured in the culture medium containing the cell factors, then the obtained CIK cells are cultured in the culture medium containing the cell factors and the PP2A inhibitor, the amplification efficiency of the CIK cells is improved through the PP2A inhibitor, and the proportion of CD3 + CD56 + cells in the CIK cells is increased; according to the invention, a cell signal transduction pathway regulator PP2A inhibitor is ingeniously introduced, and culture conditions are optimized, so that the amplification efficiency of CIK cells is remarkably improved, and the proportion of functional subgroups is improved. Meanwhile, on the basis of improving the cell performance, the preparation cost of the CIK cell is relatively reduced, and the CIK cell is particularly suitable for preparing a CIK cell preparation required by adoptive immunotherapy and can be widely applied to treatment of solid tumors and blood system tumors.