1559 results about "Cell therapy" patented technology

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).

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 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 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 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.

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.

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.

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.

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 invention relates to a method for engineering transformation of cells by using scar-free annular mRNA and application of the method. Specifically, the present inventors make circular mRNA for in vitro and / or in vivo protein production based on a cyclization technique of a secondary structure of circular RNA. The annular mRNA does not contain any extra sequence except the target sequence, and is an accurate and efficient mRNA cyclization strategy, and the generated scar-free annular mRNA has the advantages of good stability, long half-life period, high protein expression total amount and the like, can be used for CAR and / or TCR related cell therapy, is especially suitable for in-vivo CAR generation cell therapy, and has a good application prospect. The compound has wide application in the field of clinical treatment of tumors, autoimmune diseases, infectious diseases and the like.

The invention relates to the field of biotechnology and cell therapy, in particular to a recombinant construct, a CAR (chimeric antigen receptor) modified cell and application. On the objective basis of different antigen target spots, such as CD19, CLDN18.2 or BCMA and other different antigen target spots corresponding to abnormal expression of tumors, the target spots are used as target spots for clinical treatment; under the condition that the expression of the chimeric antigen is not changed, two cell factors are secreted synergistically; the long-term treatment effect of immune cells is enhanced, and meanwhile, the treatment risk is reduced.

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.

The present disclosure provides methods for genetically engineering T cells, such as CD4+ T cells, for use in cell therapy. In some aspects, the provided methods include one or more steps for incubating the cells under stimulating conditions, introducing a recombinant polypeptide to the cells through transduction or transfection, and cultivating the cells under conditions that promote proliferation and / or expansion. In some aspects, the incubation and / or the cultivation is performed in the presence of recombinant IL-2. In some aspects, the provided methods are an efficient, reliable means to produce genetically engineered T cells with a high degree of success.

Compounds that either produced a higher proportion or greater absolute number of phenotypically identified nave, 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 belongs to the technical field of biological medicines, and particularly relates to an antigen peptide library for inducing tumor specific immune response, the antigen peptide library comprises eight antigen peptides, and the amino acid sequences of the eight antigen peptides are respectively shown as SEQ ID NO.1-SEQ ID NO.8. The invention further discloses a preparation method of the antigen peptide library. The antigen peptide has high immunogenicity and can effectively stimulate and induce generation of specific cytotoxic T lymphocytes when being loaded on antigen presenting cells, in-vitro killing experiments show that CTL cells induced and activated by loading new antigen DC have a high tumor killing effect, and the cell killing activity of the CTL cells is 90% or above. When model mice are treated by adoptive T cell back-transfusion of CTL cells induced by the new antigen peptide library, the tumor volume can be effectively reduced, the survival rate of the tumor can be remarkably increased, and good treatment potential is achieved.

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 invention relates to a target cell in-vitro sorting method for cell therapy, and belongs to the technical field of cell therapy. According to the method, the cleaning solution containing EGTA, EDTA, alpha-casein and prostaglandin is used, so that the sorting method with high living cell recovery efficiency is obtained; and cell therapy can be better realized.

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 herein are compositions, kits, and methods for manufacturing immunoglobulin- related compositions (e.g., antibodies or antigen binding fragments thereof) that can bind to the LAMP5 protein, and uses thereof. Additionally, provided herein are compositions, kits, and methods for manufacturing cells for adoptive cell therapy comprising engineered immune cells that express a LAMP5-specific receptor (e.g., a LAMP5-specific chimeric antigen receptor), and uses thereof. Additionally, provided herein are methods for identifying the risk of cancer in individuals of African American descent based on elevated LAMP5 levels in cancer cells.

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.