2191 results about "Cell therapy" patented technology

The present disclosure relates in some aspects to methods, cells, and compositions for preparing cells and compositions for genetic engineering and cell therapy. Provided in some embodiments are streamlined cell preparation methods, e.g., for isolation, processing, incubation, and genetic engineering of cells and populations of cells. Also provided are cells and compositions produced by the methods and methods of their use. The cells can include immune cells, such as T cells, and generally include a plurality of isolated T cell populations or types. In some aspects, the methods are capable of preparing of a plurality of different cell populations for adoptive therapy using fewer steps and / or resources and / or reduced handling compared with other methods.

Provided are genetically engineered induced pluripotent stem cells (iPSCs) and derivative cells thereof that express C-X-C chemokine receptor type 4 (CXCR4). Also provided are uses of the CXCR4 positive iPSCs or derivative cells thereof for allogenic cell therapy.

The present disclosure provides systems and methods for processing cells. The systems of the present disclosure may include a compartment, a three-dimensional (3D) matrix, a fluid flow path, an analysis unit, a preservation unit, or any combination thereof. The methods of the present disclosure may process cells via, for example, expansion, culturing, gene delivery, activation, or any combination thereof. The systems and methods described herein may be useful for producing cell products including, for example, cell therapy products.

Disclosed herein are compositions and methods for modulating T cells. For example, the compositions and methods may be used to increase memory T cells. The compositions and methods may increase the expression or protein level of a transcription factor selected from TGIF2LX, TGIF1, TGIF2, FOS, HNF4A, KLF8, NFKBIZ, CARF, EBF3, HMX3, LHX4, LMX1A, PLAG1, PLAGL1, POU2F3, SOX14, TFAP2D, and WT1, or a combination thereof. The compositions and method may be used in combination with Adoptive T Cell Therapy (ACT) to enhance the ACT.

A three-dimensional scaffold for use in engineered tissue includes a repeated 3D geometry; and at least one of a hydrogel, a biocompatible polymer, and a bioprintable polymer. The repeated 3D geometry may include an open geometry including a plurality of interconnected nodes configured to be seeded with living cells. The scaffold may be formed via bioprinting. The three-dimensional scaffold may also be used for (1) 3D tissue modelling (for liver, kidney, gut, pancreas, heart, lung, spleen, etc.), (2) disease modeling of different tumor types such as breast, colorectal, lung, liver, brain, ovarian and others, (3) drug testing / therapeutic screening of small molecule drugs, peptides, proteins, antibodies, ADCs, gene therapies, RNA-based therapeutics, cell therapies, and tissue therapies, and (4) therapeutic / drug delivery (i.e., via delivery device that can be used to control drug release based on different patterns).

Provided herein are combination therapies involving administration of an immunotherapy involving a cell therapy, such as a T cell therapy, and an inhibitor of gamma secretase. Also provided are methods for engineering, preparing, and producing the cells, compositions containing the cells and / or gamma secretase inhibitor, and kits and devices containing and for using, producing and administering the cells and / or gamma secretase inhibitor, such as in accord with the provided combination therapy methods.

Disclosed herein are compositions and methods for modulating T cells. For example, the compositions and methods may be used to increase memory T cells. The compositions and methods may increase the expression or protein level of a transcription factor selected from THAP6, DMRT3, MEF2B, PAX2, ATOH7, KLF2, KLF1, TWIST1, NKX6, and FEV, or a combination thereof. The compositions and method may be used in combination with Adoptive T Cell Therapy (ACT) to enhance the ACT.

The present disclosure relates in some aspects to methods, cells, and compositions for preparing cells and compositions for genetic engineering and cell therapy. Provided in some embodiments are streamlined cell preparation methods, e.g., for isolation, processing, incubation, and genetic engineering of cells and populations of cells. Also provided are cells and compositions produced by the methods and methods of their use. The cells can include immune cells, such as T cells, and generally include a plurality of isolated T cell populations or types. In some aspects, the methods are capable of preparing of a plurality of different cell populations for adoptive therapy using fewer steps and / or resources and / or reduced handling compared with other methods.

The invention includes improved methods and compositions for detecting specific insertion of a chimeric antigen receptor (CAR) sequence in the desired locus in the genome of a cell. Methods are useful as quality control for CAR-T cell or CAR-NK cell preparations.

The invention provides compositions and methods for manufacturing adoptive cell therapies. In particular embodiments, the invention provides methods of harvesting populations of cells, isolating and activating PBMCs, expanding T cells, and administering the T cell therapeutic to a subject in need thereof.

Provided is a lipid formulation which is substantially free from cholesterol and which is mixed with nucleic acid to form lipid nucleic acid nanoparticles which are capable of transfecting cells of the immune system in a less destructive manner than electroporation.

The present invention discloses a nano antibody against BCMA and its preparation method and application, and relates to the field of biomedical technology. The present invention uses CRISPR / Cas9 technology to knock out B2M and TRAC genes in T cells to prepare universal CAR-T cells; the nano antibody targeting BCMA and the natural ligand SIRPα extracellular N-terminal V region of CD47, the transmembrane region of CD28, the intracellular signal region of 4-1BB and the intracellular signal region of CD3ζ are connected in series to form a dual-targeted chimeric antigen receptor for the treatment of multiple myeloma, so as to solve the high recurrence problem faced by CAR-T cell therapy in the treatment of multiple myeloma. The universal CAR-T cells prepared by the present invention have strong killing activity against multiple myeloma cells, effectively improve the treatment effect, and provide a key material for the subsequent development of adoptive immunotherapy with high efficiency and lasting anti-tumor activity.

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 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 discloses an anti-TP53 mutation T cell receptor and application thereof, the T cell receptor comprises specific alpha chain and beta chain variable domains, and the complementary determining region (CDR) sequence is shown as SEQ ID NO: 9-14. The TCR has the core advantage that the TCR has excellent broad-spectrum recognition capability, can target six different amino acid substitutions (A, G, I, N, S and T) at the R249 site, and effectively deals with tumor heterogeneity and mutation difference between patients. Aiming at high-frequency HLA-B * 07: 02 alleles in people, the TCR lays a foundation for developing TCR-T cell therapy covering a wide range of people, and has great clinical application value and market potential in treatment of various solid tumors carrying TP53 R249 hotspot mutation, such as liver 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.

Provided herein are compositions and methods for adoptive cell therapy comprising engineered immune cells that express a tumor antigen-targeted chimeric antigen receptor and a prodrug converting enzyme.

The present invention relates generally to the field of site-specific DNA recombination mediated by lambda integrase, and more specifically, to a method for producing eukaryotic cells and cell lines comprising a genomic landing pad for lambda integrase-mediated recombination, and methods of using the eukaryotic cells themselves and subsequently their use in lambda integrase mediated recombination and as bioreactors for cell therapy.

The invention relates to the technical field of cell activity detection, in particular to an umbilical cord blood stem cell activity detection method and system.The method comprises the following steps that cells are separated from a fresh umbilical cord blood sample in a sterile environment, cell activity preliminary identification is conducted on the separated stem cells, and a cell activity evaluation result is generated; screening cells with activity meeting a preset standard, and performing function evaluation to obtain a screened cell set. According to the method, through accurate preliminary cell viability identification and function evaluation, the scheme optimizes the selection standard of umbilical cord blood stem cells, effectively screens out cells with high regeneration capacity and biological activity, enhances the success rate of cell therapy and reduces the risk caused by improper selection, and by analyzing the gene regulatory network of the screened cells, the cell therapy effect is improved. The functionality is accurately evaluated, it is ensured that only the most potential cells are used for subsequent culture and clinical application, the curative effect and the product quality are remarkably improved, and the culture efficiency and the success rate are further improved through an optimized culture scheme and a monitoring system.

The invention discloses a therapeutic nano-vesicle preparation rich in mitochondrial functional protein, a preparation method of the therapeutic nano-vesicle preparation and application of the therapeutic nano-vesicle preparation in treatment of radioactive skin injury. The preparation method comprises the following steps: culturing, amplifying and cleaning umbilical cord mesenchymal stem cells, dispersing the umbilical cord mesenchymal stem cells in a suspension, mechanically extruding the umbilical cord mesenchymal stem cells into a crude solution through a multistage aperture polycarbonate membrane, and centrifuging, concentrating and purifying the crude solution to obtain the preparation. The preparation has the remarkable advantages that local administration can be realized, inflammation can be quickly inhibited, oxidative stress is reduced, and a repair pathway is activated, so that the preparation is suitable for treating acute radioactive skin injury; the preparation method is easy to standardize and scale, high in stability and convenient for emergency storage and delivery, and avoids the defects of cell therapy; a plurality of targets such as immune inflammation, oxidative stress and the like can be synergistically regulated, the biological effect of hUMSCs is simulated and partially replaced, and the limitation caused by the cell survival rate and the microenvironment dependency is avoided; the key function of hUMSCs is covered in function, and the clinical feasibility, safety and emergency suitability of the application level are higher.

The invention relates to the technical field of biological medicine, in particular to the field of cell therapy, and particularly relates to application of STAR and immune cells comprising the STAR to treatment and / or prevention of tumors, an antigen binding region of the STAR comprises one or more than two of an antibody, a ligand or an antibody fusion body which binds to LILRB4, the antibody such as scFv or VHH, and the ligand and the antibody fusion body can be combined with the LILRB4. Wherein the LILRB4 is used as a tumor antigen and / or a receptor in an immunosuppressive active cell. According to the invention, the targeted killing effect of immune cells on tumors is enhanced by targeting tumor cells and / or reducing immune escape caused by immunosuppressive active cells.

The invention relates to the field of tumor cell therapy, in particular to application of T lymphocyte chimeric with a B7-H3 receptor to treatment of head and neck tumors, and provides an anti-B7-H3 scFv, the scFv comprises a heavy chain variable region and a light chain variable region, the heavy chain variable region comprises an HCDR region and an HFR region, and the light chain variable region comprises an LCDR region and an LFR region; compared with a wild type scFv sequence, the scFv sequence has the advantage that a plurality of amino acids with positive charges in the HFR region and / or the LFR region are mutated into amino acids without charges. According to the invention, positive charge plaques on the CAR surface of an scFv sequence of a B7-H3 human-derived monoclonal antibody MGA271 are changed in a charged amino acid mutation manner, so that a B7-H3. CAR-T cell is optimized, and it is proved that the B7-H3. CAR-T cell optimized by PCP can effectively kill B7-H3 positive tumor cells in vivo and in vitro; and a new method and thought are provided for clinical targeted treatment of B7-H3 positive solid tumors.

Provided is use of a new immune checkpoint PIEZO1 pathway in tumor T-cell therapy. A PIEZO1 inhibitor can be used for treating cancers, improving the killing ability of T cells, and improving the therapeutic effect of an immune checkpoint inhibitor.

The invention belongs to the field of biomedical materials, and particularly relates to a PBAE-DOPE-PEG2000 polymer-lipid nanocomposite and a preparation method and application thereof.The preparation method comprises the steps that a dimethyl sulfoxide-ethanol solution formed by mixing DOPE-PEG2000 lipid and PBAE serves as an oil phase, a sodium acetate / acetic acid buffer solution serves as a water phase, and the PBAE-DOPE-PEG2000 polymer-lipid nanocomposite is prepared through a microfluidic synthesis mode; the PBAE-DOPE-PEG2000 polymer-lipid nano composite material is prepared by the steps of carrying out ultrasonic treatment on the PBAE-DOPE-PEG The polymer-lipid nano composite material can efficiently load exogenous genes, the surface performance of the polymer-lipid nano composite material is changed and the stability of nano particles is improved by introducing DOPE-PEG2000 lipid, membrane fusion can be promoted, the risk of lysosome degradation is reduced, the transfection process of the exogenous genes in recipient cells is accelerated, and efficient expression in 293FT cells is realized. The efficient transfection of the polymer-lipid nanocomposite material is expected to show important application prospects in immune cell therapy or tumor cell therapy.

Disclosed herein are methods of making and using an expanded population of γδ T cells. Disclosed herein is an allogeneic γδ CAR T-cell therapy.

The present disclosure provides CARs comprising a human mesothelin (MSLN) binder, related polynucleotides and vectors, engineered cells, pharmaceutical compositions, and cell therapies.

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.

The present invention is based on the demonstration that bacteria of the Akkermansia genus improve the response to CAR T-cells therapy. According to the invention, Akkermansia bacteria are administered to patients treated with CAR T-cells, especially if their gut microbiome was devoid of such bacteria before administering said CAR T-cells.

The invention discloses a Parkinson's disease animal model, a construction method and application, and relates to the field of animal genetic engineering and disease model construction. According to the model, seven mutation sites related to the human familial Parkinson's disease are introduced behind an initiation codon of a fourth exon of an endogenous SNCA gene, and the mutation sites are A18T, A29S, A30P, E46K, H50Q, G51D and A53T and have genotypes related to the human familial Parkinson's disease. The pig model shows nigra dopaminergic neuron reduction and cortical neuron reduction in the newborn period, and the core pathological process of the human Parkinson's disease can be systematically reproduced. The model can be widely applied to Parkinson's disease pathogenesis research, drug screening and cell therapy effect evaluation, and has important scientific research and preclinical application values.

An antigen peptide is provided specifically for treating individuals suffering from ovarian cancer, preferably based on BRCA1 gene c. 5470_5477del8 mutation. It is selected from amino acid sequences of SEQ ID NO. 1 to SEQ ID NO. 6, or derived by substitution, deletion and / or addition of at least one amino acid. The neoantigen polypeptides of the present disclosure can significantly activate T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro, stimulating the release of the cytokine IFN-y, indicating notable immunogenicity. This enhances T lymphocytes' ability to target and kill cancer cells from ovarian cancer patients carrying the BRCA1 gene c. 5470_5477del8 mutation. Additionally, the antigen peptide can activate and expand human T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro for adoptive cell therapy. The antigen peptide of the present disclosure addresses the gap in personalized antigen peptide therapies for ovarian cancer patients with BRCAl-c. 5470_5477del8 somatic mutations.