143 results about "Cell therapy" patented technology

The disclosure provides anti-CD70 antibodies, antigen binding fragments thereof, chimeric antigen receptors (CARs) and engineered T cell receptors (TCRs) comprising an antigen binding molecule that specifically binds to CD70, polynucleotides encoding the same, and in vitro cells comprising the same. The polynucleotides, polypeptides, and in vitro cells described herein can be used in an engineered TCR and / or CAR T cell therapy for the treatment of a patient suffering from a cancer. In one embodiment, the polynucleotides, polypeptides, and in vitro cells described herein can be used for the treatment of multiple myeloma.

The present application belongs to the field of cell therapy and immunotherapy, and provides a genetically engineered human trophoblast, a preparation method and application thereof. The human trophoblast takes K562 cells as starting cells, and stably expresses membrane-bound interleukin 21, CD137 ligand and Delta-like ligand 1 after genetic engineering. The constructed K562 three-factor trophoblast can significantly improve the expansion efficiency, activation state and functional stability of NK cells and γδT cells. The synergistic mechanism includes enhancing the proliferation, cytotoxicity and stemness maintenance of NK cells and γδT cells through STAT3, NF-κB and Notch signaling pathways, respectively. The human trophoblast has the advantages of good expression stability, significant functional enhancement, and high activity after freezing and recovery.

The present disclosure relates generally to methods of making a population of trispecific CAR-expressing immune cells that provide several improvements over existing manufacturing methods, thereby enabling production of a robust supply of clinically useful CAR T-cell therapies.

Various embodiments of the invention provide binding agents for glypican-3 (GPC3), including antibodies or antigen-binding fragments thereof that bind to GPC3 and antigen recognizing receptors (e.g., CARs) that target GPC3 including cells that express GPC3. Embodiments of the i n vention also provide cells comprising such binding agents such as CAR T-cells, therapeutic compositions comprising such cells and methods of using one or more of the binding agents, cells or therapeutic compositions for the treatment of diseases or disorders associated with GPC3 expression such as various neoplastic diseases or disorders (e.g., hepatocellular carcinoma). Various embodiments of the invention also provide methods and systems for treati ng hepatocellular carcinoma (HCC) utilizing a combi nation of radiofrequency (RF) ablation and GPC3-targeted cell therapy. In certain embodiments, immune modulators, such as checkpoint inhibitors, may be co-administered to potentiate immune responses. Additionally, compositions and kits comprising RF ablation devices and GPC3-targeted cell therapy formulations are provided.

The present invention provides for chimeric antigen receptor constructs capable of being expressed in dendritic cells (DCs), and DCs modified to express one or more chimeric antigen receptors (CARs) as well as compositions comprising these modified DCs and methods of stimulating an adaptive immune response in a subject. The intracellular domain of the CAR comprises a toll-interleukin receptor (TIL) intracellular signalling domain and a costimulating domain selected from CD3 signalling domain, CD28 signalling domain and a combined CD28 and CD3 signalling domain.

Embodiments of the disclosure include methods and compositions related to modulation of bone using particular fibroblasts. The modulation includes reducing osteoclast activity and / or activation and / or stimulating osteoblast activity. In particular cases, bone is modulated in an individual with a bone condition, such as osteoporosis. Particular fibroblasts may be delivered to reduce inflammatory cytokine production including RANK ligand.

The application discloses application of mesenchymal stem cell spheroids in preparation of a preparation for treating osteoarthritis, and relates to the technical field of cell therapy and osteoarthritis treatment, and specifically comprises mesenchymal stem cell spheroids with an average diameter of 120-180 mu m and a solution containing 0.5%-10% human serum albumin. The cells are prepared into 120-180 mu m cell spheroids, and the solution containing specific concentration human serum albumin is used as a carrier, so that the cell survival rate is stabilized at more than 90%, and high-activity delivery is realized; the optimized size ensures smooth injection and long-term retention in the joint cavity, and overcomes the shortcoming that single cells are easily removed; after joint cavity injection, the preparation can synergistically promote bone reconstruction and cartilage repair, and produces clear curative effects such as bone mass increase of more than 30%, cartilage degeneration score reduction of more than 50%, and the like, which are quantifiable and verifiable, so that a stable, long-acting and curative drug preparation and application scheme are provided for osteoarthritis treatment.

The process provided in this invention transfects primary cells with gene editing reagents using a high-volume gas-permeable cell culture device and a flow-through electroporation device under conditions that improve gene editing performance, cell yield, and drug (DP) quality characteristics for cell therapy applications. As demonstrated in the examples, primary cells edited according to the process provided herein achieved improved double-strand break (DSB) formation rates, increased frequency of homology-directed repair (HR) and non-homologous end joining (NHEJ) combinations, increased frequency of bi-allelic and mono-allelic HR events, improved cell viability, proliferative capacity, and cell fitness after gene editing, and reduced manufacturing time.

This product is a work cell for cell therapy manufacturing, automating the entire manufacturing process, including cell concentration, separation, activation, gene transfer using viral vectors or electroporation, expansion culture, filling, finishing, and formulation. This product can provide a self-contained cleanroom environment with a robotic work cell, all within the size of a conference room or a small pickup truck.

Described herein are multicistronic expression systems that encode chimeric proteins, specifically membrane-cleavable chimeric systems and chimeric antigen receptors for administration in combination with the cytokine IL2 for treating a subject having cancer. Also described herein are nucleic acids, cells, and methods directed to the same. Also described herein are methods of stimulating a cell-mediated immune response to a tumor, reducing tumor volume, or providing an anti-tumor immunity in a human subject in need thereof, the methods comprise administering to a subject multiple administrations of an immunoresponsive cell encoding a controlled release cytokine.

Methods are provided for generating unlimited immune cells with increased lifespan and high proliferation rate by modifying them to express BCL6 and genes that promote cell survival. Further methods are provided for generating and using said unlimited immune cells to treat diseases such as cancer.

This cell-based formulation contains SSEA-3-positive pluripotent stem cells derived from mesenchymal tissue of a living body or derived from cultured mesenchymal cells. This cell-based formulation is characterized in that the formulation is for administration to address diseases and / or post-acute sequelae caused by SARS-CoV-2 infection. The present invention makes it possible to provide a cell-based formulation that contains pluripotent stem cells and is used for treating and / or preventing SARS-CoV-2 infection-caused diseases such as pneumonia and pulmonary fibrosis and SARS-CoV-2 infection-caused post-acute sequelae such as olfactory dysfunctions.

Provided herein are methods and uses of combination therapies involving a GPRC5D-targeted cell therapy comprising a chimeric antigen receptor (CAR) containing an extracellular antigen binding domain that binds to G Protein-Coupled Receptor Class C Group 5 Member D (GPRC5D) and a combination agent, e.g., a bispecific antibody, for treating a subject having a cancer, such as multiple myeloma, as well as related methods, uses, and articles of manufacture.

The present invention relates to compositions comprising photoreceptor precursor cells (PRPs), as well as methods of generating the composition of PRPs and methods of using the composition of PRPs for regenerative cell therapy.

This invention discloses a culture medium, preparation method, and culture method for the industrial-scale preparation of mesenchymal stem cells, belonging to the field of cell therapy technology. The culture medium comprises a basal medium, cell growth factors, cell proliferation promoters, a vitamin mixture, a nucleoside mixture, and an amino acid mixture; wherein the cell growth factors are selected from one or more of TGF-β, bFGF, VEGF, PDGF, EGF, and IGF. Through the synergistic effect of the composite nutrient system, this invention significantly improves the proliferation rate and cell viability of mesenchymal stem cells, maintains stem cell stemness, trilineage differentiation ability, and secretion levels of key cytokines (VEGF, HGF, TGF-β, IL-10, etc.); it can be stably and continuously passaged up to the 15th generation without abnormal changes in genetic material. This culture medium contains no animal-derived components, has high batch-to-batch stability, and is cost-controllable, making it suitable for GMP-level large-scale industrial preparation of mesenchymal stem cells from various sources such as umbilical cord, bone marrow, adipose tissue, and placenta.

This invention belongs to the field of biomedical technology, specifically relating to lipid nanoparticles, their preparation method, and their application in immune cell delivery. This invention introduces amino acid-derived lipids as a fifth component into a preferred four-component formulation. Furthermore, through screening of the nitrogen-to-phosphorus ratio, the proportion of amino acid-derived lipids introduced, and the type of amino acid-derived lipids, novel lipid nanoparticles capable of efficiently delivering primary immune cells are selected. The delivery carrier described in this invention can significantly improve the delivery efficiency to primary immune cells, especially NK cells, providing a safe and efficient tool for the engineering of immune cells and their clinical application in immune cell therapy.

This invention discloses a multifunctional engineered NK cell, its construction method, and its applications. This NK cell co-expresses a membrane-bound targeted cytokine complex and a secretory bispecific nanobody via a single-carrier system. The membrane-bound complex uses an anti-PD-L1 single-domain antibody to directionally anchor IL-15 / IL-21 to the cell membrane surface and utilizes synaptic recruitment to achieve high-level enrichment of cytokine signals at the immune synapse, enabling precise paracrine secretion of cytokine signals. The secretory bispecific antibody mediates specific cytotoxicity by transdirectionally linking the NK cell activation receptor NKp46 with the tumor-associated antigen B7-H3. Experiments have demonstrated that the engineered NK cells constructed in this invention significantly enhance the killing efficacy against PD-L1 or B7-H3 positive tumor cells while maintaining a high P2A cleavage rate, and the synergistic index shows a significant synergistic effect. This invention effectively overcomes the technical shortcomings of traditional NK cell therapy, such as systemic cytokine toxicity and tumor antigen escape, providing a novel strategy for immunotherapy of solid tumors.

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 technical field of biological medicine, and particularly relates to application of a KAT5 inhibitor in a medicine for enhancing the immunotherapy effect of natural killer cells, and a medicine for enhancing the immunotherapy effect of natural killer cells. The KAT5 inhibitor comprises at least one of Nu9056, TH1834 and MG149. The KAT5 inhibitor can inhibit the recruitment of a transcription factor SP1 to an ADAM10 promoter, reduce the transcriptional activity of ADAM10, reduce the expression of NKG2D ligands on the cell surface, and thus enhance the sensitivity of tumor cells to NK cell killing. The application first discloses a new mechanism in which KAT5 regulates an ADAM10-NKG2D signal axis through an epigenetic mechanism, and proves that the KAT5 inhibitor can significantly enhance the immunotherapy effect of NK cells in vitro and in vivo. The application provides a brand-new target and strategy for developing a new immunosensitizer and a combined cell therapy.

Provided herein are CD70-targeted chimeric antigen receptors (CARs), genetically engineered cells such as T cells containing the same, and related methods and uses of the genetically engineered cells in allogeneic cell therapy. Also provided are T cells that are genetically engineered with a CAR, such as a CD70-targeted CAR, and are further genetically engineered by one or more strategies to reduce host immune recognition of the engineered T cells, such as by heterologous expression of one or more additional transgenes and by genetic disruption to reduce or eliminate expression or one or more endogenous protein. Also provided are methods of making and using the engineered T cells for cell therapy, including in connection with cancer immunotherapy comprising adoptive transfer of the engineered T cells.

This invention discloses the application of substances that increase LSH content or activity in improving heterochromatin stability and enhancing the efficacy of cell therapy, belonging to the field of biomedical technology. This invention, through overexpression of LSH in IMR90 fibroblasts and T lymphocytes, successfully achieved for the first time complete inhibition of DNA methylation loss in heterochromatin regions during cell expansion. The innovative research results of this invention strongly demonstrate that the insufficient DNA methylation maintenance efficiency caused by the dense chromatin environment in heterochromatin regions is the reason for the continuous loss of DNA methylation during sustained cell expansion. Overexpression of LSH can effectively improve the DNA methylation maintenance efficiency in heterochromatin regions to prevent DNA methylation loss, thereby improving several phenotypic defects caused by sustained cell expansion. This provides a new strategy for effectively maintaining cell function in adoptive cell therapy and has broad application value in enhancing the efficacy of various cell therapies.

The present invention relates to the field of cell therapy. Disclosed are a fibroblast activation protein-targeting CAR T-cell, a preparation method therefor, and an application thereof. A CAR T-cell can be prepared by introducing an FAP-targeting chimeric antigen receptor (CAR) into a T lymphocyte, wherein the CAR in the CAR T-cell comprises a signal peptide, an antigen-binding domain, a hinge region, a transmembrane domain, a co-stimulatory signaling region, and a CD3 signaling domain. The CAR T-cell specifically recognizes the FAP by means of a single-chain variable fragment (scFv), which activates an intracellular signaling pathway, releasing cytokine IFN-γ, and exhibiting a cytotoxic effect on FAP+ cells, thereby achieving specific depletion of FAP+ cells at a lesion site. The CAR-T cell can be used for treating diseases characterized by upregulated FAP expression, such as fibrosis (pulmonary fibrosis, hepatic fibrosis, cardiac fibrosis, renal fibrosis, etc.), arthritis, autoimmune disorders (Crohn's disease, rheumatoid arthritis, etc.), and cardiovascular diseases, and demonstrates tremendous application potential and commercial value.

The invention relates to an activating composition comprising a cell, which may be any cell type used for cell therapy, wherein the cell is activated by a chemotherapy agent. Further, there is provided an activating composition comprising a supernatant of a composition comprising a cell, which may be any cell type used for cell therapy, wherein the cell is activated by a chemotherapy agent and wherein the supernatant is used as a therapy. The invention further provides methods for treating or preventing a disease or a condition comprising the use of the activated composition.

The present application relates to a preparation method and application of photoreceptor precursor cells of human embryonic stem cell-derived retinal organoids, and belongs to the field of biotechnology and stem cell engineering. The present application constructs a lentiviral vector carrying an exogenous target gene and infects human embryonic stem cells to obtain a stable expression of engineered stem cell clone group by screening; the clone group is subjected to three-dimensional differentiation, and sequentially undergoes the formation of a blastoid, neural epithelial induction and retinal layering stage to obtain a retinal organoid; finally, the co-expression of photoreceptor precursor cell markers and exogenous genes in the organoid is identified. The present application realizes stable integration of genes at the source of stem cells, avoids the problem of low infection efficiency in the later stage, and provides a complete standardized scheme from gene modification, directional differentiation to function verification. The engineered photoreceptor precursor cells obtained by the method have important application value in the construction of retinal disease models, drug screening and cell therapy development.

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.

This invention discloses an in-situ constructed FAP-targeting CAR-T nanoliposome delivery system, its preparation method, and its applications, belonging to the field of biomedical technology. This invention provides a biocompatible nanoliposome delivery system whose surface is modified with a CD3 antibody that can capture T cells through circulation, delivering plasmid DNA encoding FAP-CAR into the T cells, thus in-situ transforming T cells into CAR-T cells in vivo. The nanoliposome delivery system provided by this invention can significantly alleviate myocardial fibrosis caused by myocardial infarction and restore cardiac function, providing a research basis for the clinical application of CAR-T cell therapy based on in-situ nanoengineering in myocardial infarction.

The present disclosure relates to cell processing technology. As an example, a cell processing system can include a plurality of sample processing devices configured to process patient samples and a plurality of readers associated with the plurality of sample processing devices, respectively, wherein each reader is configured to read information from a tracking device associated with a respective patient sample. The system can also include a controller that uses information from the readers to provide an estimated completion time for a patient sample based on availability of the sample processing devices.

Expression constructs encoding chimeric antigen receptors and DAP10 recombinant polypeptides, engineered immune cells, and methods of use thereof are provided. Further provided are methods for activation and expansion of cells for therapeutic use, in particular for chimeric antigen receptor-based immune cell immunotherapy.