1247 results about "Cell therapy" patented technology

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.

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.

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 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.

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.

Provided herein are chimeric receptors, including chimeric antigen receptors (CARs), comprising BCMA-binding molecules, including anti-BCMA antibodies and antigen-binding fragments thereof, including heavy chain variable (VH) regions and single-chain antibody fragments, and encoding polynucleotides. In some embodiments, the anti-BCMA chimeric receptors specifically bind to BCMA. Among the anti-BCMA-binding molecules are human antibodies, including those that compete for binding to BCMA with reference antibodies, including a non-human reference antibody. Also provided are genetically engineered cells expressing the CARs and uses thereof including in adoptive cell therapy.

The invention discloses a nano magnetic bead for specific capture of DNA (deoxyribonucleic acid) of bacteria and fungi, a preparation method of the nano magnetic bead and a rapid sterile detection method of a cell therapy product. The method comprises the following steps: S1, coating Fe3O4 with polydopamine to form a modified Fe3O4 magnetic bead; s2, compounding the MOF shell layer to the modified Fe3O4 magnetic beads to form Fe3O4-coated MOF magnetic beads; s3, gold nanoparticles are anchored to the Fe3O4 (at) MOF magnetic beads to form Fe3O4 (at) MOF (at) Au magnetic beads; and S4, modifying the Fe3O4 (at) MOF (at) Au magnetic bead with a specific capture probe aiming at DNA of bacteria and fungi to form a Fe3O4 (at) MOF (at) Au-Probe probe magnetic bead. The modified DNA probe disclosed by the invention can efficiently capture free bacteria and fungus nucleic acid fragments in a sample, so that template enrichment is realized.

A drug delivery platform providing flexible fine tune of cell therapy is disclosed herein. Particularly, an engineered fusion protein is coupled with a high affinity ligand carrying at least one payload of drug to be internalized by the transplanted cell to observe or regulate transplanted cell therapy effects.

The present invention relates to a method for in vitro sorting of target cells for cell therapy, belonging to the technical field of cell therapy. The present invention utilizes a washing solution containing EGTA, EDTA, α-casein, and prostaglandins to achieve a sorting method with high viable cell recovery efficiency, thereby enabling better cell therapy.

Provided are expression constructs encoding chimeric antigen receptor and DAP10 recombinant polypeptide, engineered immune cells, and methods of use thereof. Further provided are activation and expansion of cells for therapeutic uses, especially for chimeric antigen receptor-based immune cell immunotherapy.

Disclosed are VHH chimeric antigen receptors (VCARs), VCAR transposons encoding VCARs of the disclosure, cells modified to express VCARs of the disclosure, as well as methods of making and methods of using the same for adoptive cell therapy.

The present disclosure relates generally to compositions and methods for improving T cell therapy. In particular, the disclosure provides polypeptides and recombinant nucleic acid constructs and / or recombinant nucleic acids encoding polypeptides having mutations capable of effecting altering T cell signaling, cytokine production, and / or in vivo persistence of therapeutic T cells comprising the mutations in tumors. The T cell signaling may be carried out by the NFAT, NF-[kappa] B, and / or AP-1 pathway. The disclosure also provides vectors and cells comprising the polypeptides and / or recombinant nucleic acid constructs and / or recombinant nucleic acids of the disclosure, as well as methods of making T cells for use in cell therapy, and methods of identifying mutations useful for improving T cell therapy.

Compounds that either produced a higher proportion or greater absolute number of phenotypically identified naïve, stem cell memory, central memory T cells, adaptive NK cells, and type I NKT cells are identified. Compositions and methods for modulating immune cells including T, NK, and NKT cells for adoptive cell therapies with improved efficacy are provided.

The invention relates to the technical field of cell culture. The invention provides a mesenchymal stem cell culture medium without animal-derived components and application of the mesenchymal stem cell culture medium. The culture medium comprises a basic culture medium and an additive, the additives comprise FGF-2, IGF-1, glutamine, folic acid, serotonin, cholesterol, arachidonic acid, an HEPES buffer solution, sodium bicarbonate, SCF, TGF-beta, PDGF, ascorbic acid and transferrin. The mesenchymal stem cell culture medium disclosed by the invention is completely free of animal-derived components, and meets the requirements of FDA / EMA clinical-grade cell therapy products. The culture medium can support high-density amplification of mesenchymal stem cells, the activity of passage cells is effectively improved, and the amplification time is shortened. The method has remarkable significance in improving the amplification efficiency of the mesenchymal stem cells and promoting and applying factory growth.

The invention discloses a method for extracting mesenchymal stem cells from urine. The method comprises the following steps: (1) sampling and inoculating urine; (2) amplification and passage of mesenchymal stem cells; (3) identifying the urine stem cells; and (4) a cryopreservation and resuscitation method of the urine stem cells. And performing biological phenotype identification according to the standard formulated by the International Cell Therapy Association to confirm the mesenchymal stem cells. The method is low in cost, simple and rapid, and the used culture solutions are all commercialized and are very convenient to purchase and use. The culture solution special for the stem cells is used in the first two weeks of the extraction period, after passage, when enough stem cells are obtained, the culture medium can be replaced with a common DMEM culture medium, and the manufacturing cost is greatly reduced. And secondly, the materials are simple, rapid and non-invasive, and the sample of the method for extracting the mesenchymal stem cells from urine comes from a patient, so that the problem of heterogeneity of cell sources is reduced. And a foundation is laid for stem cell treatment and gene editing treatment of genetic diseases and major difficult diseases.

Provided herein are cell surface receptors that include an extracellular binding domain, a transmembrane domain, an intracellular signaling domain, and a protease cleavage site disposed between the extracellular binding domain and the intracellular signaling domain. In certain aspects, the cell surface receptors are engineered cell surface receptors, such as chimeric antigen receptors (CARs). Also provided are cells that include such receptors (e.g., where the cells express the receptors on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the cell surface receptors, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for regulating signaling of a cell surface receptor, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable cell-based therapy to an individual.

Provided are polypeptides that include, from N-terminus to C-terminus, a chimeric antigen receptor (CAR), a protease, and a degron, where the polypeptide further includes a cleavage site for the protease disposed between the CAR and the degron. Also provided are cells that include such polypeptides (e.g., where the cells express the CAR on their surface) and pharmaceutical compositions including such cells. Nucleic acids that encode the polypeptides, cells including such nucleic acids, and pharmaceutical compositions including such cells, are also provided. Also provided are methods for controlling the expression of a CAR on the surface of a cell, and methods of using the cells of the present disclosure, including methods of using such cells to administer a regulatable CAR cell-based therapy (e.g., a regulatable CAR T cell therapy) to an individual.

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).

Described herein are engineered cytokine receptor switches that can include a signal peptide, an extracellular activator binding domain, a hinge, a transmembrane domain, and / or an intracellular signaling domain. Binding of an activator to the activator binding domain can activate cytokine signaling through the intracellular signaling domain. These cytokine receptor switches can be expressed in immune cells, sometimes in combination with a chimeric antigen receptor (CAR), to increase immune cell persistence by promoting adoption of memory-like phenotypes. Also described herein are methods of using engineered cytokine receptors in immune cell therapies, such as CAR T-cell therapy, to improve patient outcomes and prevent disease relapse.

Methods are provided for reprogramming M2-like macrophages to M1-like macrophages, which reverses the proinflammatory to anti-inflammatory shift observed during the course of certain cancers, co-administered with one or more types of engineered cells such as, without limitation, CAR T-cells, engineered natural killer cells, engineered stem cells or the like. The compounds comprise an immune modulator that targets a pattern recognition receptor of a cell and are specific to the cells of interest through the incorporation of a targeting moiety (e.g., folate or a functional fragment or analog thereof). Releasable and / or non-releasable linkers can be included and engineered to facilitate the optimal delivery of the immune modulator. The compounds and compositions can be employed in one or more methods of treatment for cancers.

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 discloses a human normal kidney immortalized cell line NRC-X1 and application thereof, and belongs to the field of microbial animal cell lines. The human normal kidney immortalized cell line is named as NRC-X1, and the preservation number is CCTCC (China Center For Type Culture Collection) NO: C2025168. The invention also discloses the application of the human normal kidney immortalized cell line NRC-X1 in a virus infection mechanism. The invention also discloses application of the human normal kidney immortalized cell line NRC-X1 in research of drug renal toxicity evaluation. The invention also discloses the application of the human normal kidney immortalized cell line NRC-X1 in bioartificial kidney and cell therapy. The invention also discloses application of the human normal kidney immortalized cell line NRC-X1 in research of kidney physiological and pathological mechanisms.

The disclosure provides inducible caspase polypeptides, compositions comprising inducible caspase polypeptides and sequences encoding the same, cells modified to express the polypeptides and compositions of the disclosure, as well as methods of making and methods of using same for adoptive cell therapy.

Systems, methods, and devices for facilitating automated manufacture of one or more cellular therapies through a graphical user interface (GUI) are provided. A method includes displaying a plurality of objects, each associated with a unit operation to be performed by a robotic cluster of a biological foundry. The method also include selecting and organizing desired objects to generate a representation of a workflow for the robotic cluster(s) to produce some or all of a cellular therapy. The representation of a workflow can be saved, retrieved and / or modified to generate an updated representation of the workflow.

The present invention inter alia relates to a chimeric transmembrane receptor comprising a polypeptide, wherein the polypeptide comprises at least one T cell immunoreceptor with Ig and ITIM domains (TIGIT) polypeptide region comprising a TIGIT extracellular ligand binding domain; further wherein the polypeptide comprises at least one non-TIGIT polypeptide region, wherein the at least one non-TIGIT polypeptide region comprises a transmembrane polypeptide region of CD2, CD40, HVEM, or CD30, and wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2, CD40, HVEM, or CD30, or wherein the transmembrane domain is from TIGIT and further wherein the at least one non-TIGIT polypeptide region comprises at least one costimulatory cytoplasmic polypeptide domain, region or motif of CD2 or CD28. The invention also relates to corresponding nucleic acids, vectors and T-cells comprising or expressing the chimeric receptors, to a pharmaceutical composition comprising the T-cells, and to methods for preparing a T-cell for immunotherapy and for treating a disease, respectively, wherein the chimeric transmembrane receptor is used.

The present disclosure provides modified cells comprising a nucleic acid encoding an agent (e.g., a detection agent, a selection agent, or a detection agent and a selection agent) inserted at an endogenous proliferation gene or off-target cell marker gene, as well as compositions, methods, uses, and kits related thereto.

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.

The presently disclosed subject matter relates to tumor infiltrated T cells induced by oncolytic virus (“OV-induced T cells”), methods of making and using said OV-induced T cells for an adoptive T-cell therapy. The presently disclosed subject matter further relates to oncolytic viruses and armed oncolytic viruses, methods of making and using said oncolytic viruses, as well as pharmaceutical compositions and kits comprising said oncolytic viruses.