49 results about "Autologous cell" patented technology

Provided herein are tumor-antigen VGLL1 specific T cell receptors. The TCR may be utilized in various therapies, such as autologous cell transplantation, to treat a cancer. Methods for expanding a population of T cells that target VGLL1 are also provided.

The present invention relates to a device for a scalable biomanufacturing platform for the production of modified cells such as CAR-modified T-cells while eliminating on-target / off-tumor toxicity and decreasing the current production cost by 500 times (per treatment), and to attendant methods. The includes a first chamber for proliferating a population of cells and a second chamber for modifying the cells to express a desired T-cell receptor antigen.

The invention discloses an autologous NK cell in-vitro culture method for improving purity and amplification multiple, and belongs to the technical field of biology. In order to overcome the defect that in-vitro large-scale amplification and activation of autologous NK cells of unhealthy people (solid tumor patients) are difficult, the autologous NK cells are obtained from peripheral blood of the patients, autologous CD3 + cells are used as trophoblast layers, the autologous NK cells of the patients are efficiently amplified in vitro, the cell purity reaches 99% or above, biosafety risks do not exist, and the autologous NK cells of the patients can be efficiently amplified in vitro. Moreover, an efficient anti-tumor effect is also shown in vivo, the bottleneck of in-vitro amplification of autologous NK cells of a patient is overcome, and a new direction is provided for cellular immunotherapy of the patient.

The present invention relates to the field of T cells and provides methods of producing autologous T cells and compositions thereof for the treatment of B-cell malignancies and other cancers. A method of making T cells expressing a cell surface receptor that recognizes a specific antigen moiety on the surface of a target cell, the method comprising enriching a population of lymphocytes; stimulating the population of lymphocytes with one or more T cell stimulators to produce a population of activated T cells, the stimulation being performed in a closed system using a serum-free culture medium; transduction of the activated population of T cells with a viral vector comprising a nucleic acid molecule encoding a cell surface receptor, producing a transduction population of T cells using single cycle transduction, the transduction being performed in a closed system using a serum-free culture medium; the transduced population of T cells is expanded for a predetermined time resulting in an engineered population of T cells, the expansion being performed in a closed system using a serum-free culture medium. The methods and processes described herein can be completed in significantly shorter time.

The present invention relates to a method for enhancing production of autologous genetically engineered T cells for use in cell therapy applications.

In the field of gene therapy, a major hurdle is the design and identification of constructs and gene therapy vectors providing therapeutic effects while displaying satisfactory safety profiles. In the treatment of Diamond-Blackfan Anemia (DBA), therapies alleviating several crucial anemia symptoms, such as blood or bone marrow cellularity, hemoglobin levels, erythrocytes levels, or platelet levels, while showing satisfactory safety profiles remain a challenge. The present invention provides constructs encoding ribosomal protein genes involved in DBA, such as genes encoding RPS19, RPS17, RPS24, RPS10, RPL35a, RPL11, RPS26, and RPL5, vectors, methods, cells, and medical uses thereof, addressing these challenges and finding particular applications in the field of autologous cell therapy treatment of DBA. Further, the present invention provides a non-genotoxic conditioning protocol for preparing a subject prior to cell therapy treatment for DBA using construct of the present invention.

CD38 is also expressed in a variety of hematological malignancies, including multiple myeloma. In the present invention, the inventors obtained a new antibody against CD38 that can be used to produce bispecific antibodies and CAR T cell populations. In particular, the inventors reported the development of Bi38-3, a new bispecific T cell engager that targets CD38 on MM cells and forms cytotoxic T cells through CD3ε. Bi38-3 lacks the Fc region of natural mAbs, which contributes to the resistance process, but triggers T cell proliferation, cytokine release, and lysis of CD38-positive MM cells in vitro. Similarly, Bi38-3 induces autologous T cells to eliminate tumor plasma cells isolated from MM patients at diagnosis and relapse. The cytotoxicity triggered by Bi38-3 is limited to cells expressing high levels of CD38 and maintains the integrity of T, B, and NK lymphocytes in vitro. Importantly, Bi38-3 rapidly reduced tumor cells in the MM1.S xenograft mouse model of human MM. In summary, the results show that the antibody of the present invention is an effective agent for specifically eliminating CD38-positive malignant cells without significantly affecting CD38-low-expressing cells, and is a promising new immunotherapy tool for treating malignant blood diseases, especially multiple myeloma.

The invention provides a pharmaceutical composition for treating triple negative breast cancer and application thereof, the pharmaceutical composition comprises beta-nicotinamide mononucleotide and an anti-PD-1 antibody, the administration mode of the beta-nicotinamide mononucleotide is oral administration or treatment of autologous CD8 + T cells of a patient by using the beta-nicotinamide mononucleotide, and the treated CD8 + T cells are transfused back into the body of the patient. In-vitro experiments and animal experiments show that the beta-nicotinamide mononucleotide and the anti-PD-1 antibody are combined for use, the activity of tumor cells is remarkably reduced, the killing capacity of CD8 + T cells is remarkably improved, the beta-nicotinamide mononucleotide can improve the effect of immunotherapy of the anti-PD-1 antibody on triple negative breast cancer, and the beta-nicotinamide mononucleotide and the anti-PD-1 antibody have a remarkable synergistic effect. The beta-nicotinamide mononucleotide and the anti-PD-1 antibody are combined for use, so that benefits of more patients are achieved, the treatment effect is improved, meanwhile, the market potential of related drugs is widened, the life quality of the patients is expected to be improved, and important innovation and commercial opportunities are brought to the medical field.

To provide methods for generating midbrain dopamine (mDA) neural progenitor cells useful for autologous cell therapy in Parkinson's disease, compositions comprising the cells, and methods of use thereof.SOLUTION: Provided is a method of producing a population of mesencephalic dopaminergic progenitor cells (mDAP), comprising the steps of providing a population of induced pluripotent stem cells (iPSC), preferably human iPSC, seeding said population of cells in discrete regions within a biological matrix hydrogel support at a density of about 5,000 to 20,000, preferably about 10,000 cells per region with a distance between said regions sufficient to maintain separation between said regions, and maintaining said cells under conditions sufficient for said iPSC to differentiate into mDAP.SELECTED DRAWING: None

The present disclosure provides an autologous cell therapy for treating a cancer. Transarterial tirapazamine embolization (TATE) therapy induces tumor necrosis, which, in combination with anti-PD-1 therapy, enhances the efficacy of anti-PD-1 through TATE-induced expansion of anti-tumor T cells activated by the anti-PD-1 antibody. PBMCs collected from TATE and PD-1 -treated patients for RNA and DNA extraction and next generation sequencing (NGS) analysis of complementarity region-3 of the TCR from T cell populations in the PBMCs show that clonal expansion of anti-tumor specific T cell receptors (TCRs) occurs. Expansion of the PBMC population for administration to a cancer patient preferentially expands the population of effector T cells targeting the tumor cells without a need for genetic manipulation.

The invention discloses a cell population as well as a preparation method and application thereof, and belongs to the technical field of biology. The cell population comprises engineered immune cells, the engineered immune cells comprise an exogenous nucleic acid, the insertion of the exogenous nucleic acid into a B2M gene fragment region causes the B2M gene to be disrupted, and the exogenous nucleic acid comprises a nucleic acid encoding a chimeric antigen receptor. The cell population destroys B2M by knocking nucleic acid encoding a chimeric antigen receptor (CAR) into a B2M locus, can be used for preparing a universal cell therapy product, and overcomes the problems that autologous T cell therapy is limited by the number and quality of T cells of a patient, and the preparation period is long.

The present disclosure relates to the technical field of biomaterials, and provides a catechol-functionalized gelatin microsphere and a use thereof in preparation of a product for inhibiting formation of subcutaneous fluid accumulation and promoting tissue repair. The catechol-functionalized gelatin microsphere designed and prepared in the present disclosure not only has wet tissue adhesion capability, but also has good liquid absorption performance and biodegradability. The results of cell experiments show that abundant interfaces of catechol-functionalized gelatin microspheres can promote cell adhesion and proliferation, and the loose structure of the microspheres can also promote cell migration. The results of chest wall defect repair experiments of New Zealand white rabbits show that the catechol-functionalized gelatin microspheres can not only inhibit formation of subcutaneous fluid accumulation, but also recruit autologous cells in situ and promote proliferation thereof and secretion of extracellular matrix (such as collagen). These results indicate that the catechol-functionalized gelatin microsphere material has clinical application potential of inhibiting the formation of subcutaneous fluid accumulation, and promoting subcutaneous tissue regeneration and wound healing.

The invention relates to the technical field of immune cells, and discloses a rat NK cell separation and multiplication culture method which comprises the following steps: screening rat PBMC cells in a CD161 + positive screening mode to obtain rat NK cells; the rat NK cells and the rat PBMC cells are mixed and co-cultured, and the working concentration of the interleukin growth factor is adjusted in stages in the culture process. In the scheme of the application, the rat NK cells obtained by separation and amplification in the peripheral blood of the rat have the characteristics of large quantity, strong functional activity, no infectious pathogen pollution and the like, and can be used as an important source of non-autologous NK cells; abundant cell sources can be provided for clinically using non-autologous NK cells to treat diseases such as malignant tumors and virus infection. Meanwhile, efficient amplification of the rat NK cells can be realized, and the obtained rat NK cells have the characteristics of high purity and high activity.

The present invention relates to the field of T cells and provides methods of producing autologous T cells and compositions thereof for the treatment of B-cell malignancies and other cancers. A method of making T cells expressing a cell surface receptor that recognizes a specific antigen moiety on the surface of a target cell, the method comprising enriching a population of lymphocytes; stimulating the population of lymphocytes with one or more T cell stimulators to produce a population of activated T cells, the stimulation being performed in a closed system using a serum-free culture medium; transduction of the activated population of T cells with a viral vector comprising a nucleic acid molecule encoding a cell surface receptor, producing a transduction population of T cells using single cycle transduction, the transduction being performed in a closed system using a serum-free culture medium; the transduced population of T cells is expanded for a predetermined time resulting in an engineered population of T cells, the expansion being performed in a closed system using a serum-free culture medium. The methods and processes described herein can be completed in significantly shorter time.

Embodiments relate to a living tissue graft derived from autologous cells used to provide support or to strengthen / reinforce compromised tissue. The living tissue graft comprises both cells and extracellular matrix (ECM) and overcomes problems related to foreign body responses to synthetic materials and rejection reactions to allograft tissue.

The invention provides a driver fatigue early warning method, device and equipment and a storage medium, and relates to the technical field of safety monitoring. The method comprises the following steps: acquiring hiPSC derived myocardial cells; placing the cells in vitro for culturing; detecting cell physiological indexes and calculating an ischemic tolerance score; determining a driving safety threshold value of the target driver; collecting current driving data; and when the current driving data reaches or exceeds a driving safety threshold value, an early warning signal is triggered. According to the method, by detecting the tolerance of the autologous cells of the driver in the simulated anoxic environment, accurate evaluation based on individual biological characteristics is achieved, and the defect that a general standard cannot adapt to individual differences is overcome. By converting the tolerance limit of the cellular level into the personalized driving safety threshold value and performing real-time monitoring, predictive alarm can be performed before physiological collapse, and the active prevention capability of sudden diseases caused by driving fatigue is remarkably improved.

The present invention belongs to the technical field of cellular anti-aging, and specifically relates to a small-molecule compound composition capable of reversing the senescence of an adult stem cell and restoring the regeneration activity thereof, and a method for reversing cellular senescence by means of using a chemical small-molecule composition and the use thereof. The composition capable of reversing cellular senescence comprises a WNT / β-catenin agonist, a TGF-β receptor inhibitor, an RAR agonist, a Smoothened receptor agonist, a multi-target inhibitor of the VEGFR and PDGFR families, a histone methyltransferase inhibitor, and a JAK1 / 2 inhibitor. The composition effectively solves the problem of the weak proliferation and regeneration potential of senescent adult stem cells, effectively reverses the senescence of the adult stem cells and maintains the intrinsic biological characteristics of the cells, and can thus improve and enhance the efficacy of clinical autologous cell transplantation therapy and cell derivative therapy.

The application provides a preparation method of autologous cell source nanovesicle loaded miRNA in intervertebral disc degeneration, and steps include: (1) adding miRNA mimics into PBS resuspension of nucleus pulposus cells; (2) using polycarbonate membrane with gradient pore size reduction and NV preparation instrument to extrude the nucleus pulposus cells, and obtaining autologous cell source NV loaded miRNA after sterilization and centrifugation; the autologous cell source nanovesicle loaded miRNA is used in preparation of drugs and complex drugs for treating intervertebral disc degeneration. The application provides a method of autologous cell source nanovesicle loaded miRNA, stress response key miRNA in intervertebral disc degeneration and biological functions thereof are recognized, and autologous nucleus pulposus cell source NV is used to load the stress response key miRNA, effective delivery of miRNA in intervertebral disc is realized, and finally the function of delaying intervertebral disc degeneration under abnormal stress load is played.

Methods for generating midbrain dopamine (mDA) neural progenitor cells useful for autologous cell therapy in Parkinson's disease, compositions comprising the cells, and methods of use thereof are provided.

Epigenetic modifications play an important role in regulating cell-specific expression patterns. Different DNA methylation signatures, for example, can be found in different tissues and even between different cell types within a particular tissue. In work leading to the present invention, the inventors found that these methylation signatures can be used to identify cfDNA tissue of origin. Moreover, these novel methylation markers can be used to detect cell, tissue or organ damage, including autologous cell, tissue or organ damage.

Compositions and methods for upregulating L1 RNA activity in a subject in need thereof are provided. The compositions include nucleic acids encoding L1 RNA or the L1 RNA, alone, or contained in an expression vector and / or further contained within osteogenic progenitor cells, for example, mesenchymal stem cells, genetically engineering to express L1 RNA. In this aspect, the compositions are used to increase L1 RNA levels for example, L1 RNA copy number in subjects in need of increasing their bone mass index. In a preferred embodiment, the bone progenitor cells are autologous cells.Compositions and methods for downregulating L1 RNA levels / activity in a subject in need thereof are also provided. The compositions include one or more agents in effective amounts to knockdown L1 RNA in a cell. The compositions can be used to treat conditions associated with ageing. A preferred agent is a L1 RNA antisense oligonucleotide.

A composition for preventing or treating cancer or infectious disease is disclosed. The composition contains, as an active ingredient, a pluripotent stem cell-derived immune cell expressing IL-7, CCL19, or a combination thereof. The composition provides a multifaceted and synergistic therapeutic effect derived from the complementary immune response of the patient's endogenous T cells and the injected natural killer cells, by administering only a therapeutically effective amount of immune cells other than T cells, specifically natural killer cells. The natural killer cells of the composition may also be co-administered with exogenous T cells to allow these different cell populations to act more intensively at the lesion site. The composition is based on the differentiation of pluripotent stem cells, specifically induced pluripotent stem cells (iPSCs) into immune cells, thus can be used to generate an unlimited supply of allogenic or autologous cells as needed.

The degradable stent is of a hollow tubular structure with the two ends open and comprises a main tube body and retention flanges at the two ends of the main tube body, the main tube body comprises a plurality of coaxially-nested sub-tube bodies, annular gaps are formed between the adjacent sub-tube bodies, the two ends of any sub-tube body are connected with the retention flanges, and a plurality of holes are formed in the tube wall of each sub-tube body; and in the radial direction of the main pipe body, the porosity of the pipe wall of the sub pipe body is gradually increased from the central axis to the periphery. The main tube body is arranged to be a plurality of coaxially nested sub-tube bodies with gradually increased porosity, an outer-layer tissue migration guiding channel is formed, the sub-tube bodies on the outermost layer of the stent preferentially induce rapid migration and colonization of autologous tissues, and a gradual mechanical supporting environment is provided for deep tissue cell ingrowth along with the sequential reduction of the porosity of the inner layer. When autologous cells construct a complete cavity tissue structure, each layer of material of the stent is gradually degraded and absorbed according to a preset gradient, and finally a natural cavity with a physiological function is formed at an implantation part, so that the risk of a secondary operation is avoided.

The present invention provides a bispecific CAR-T cell that targets BCMA and GPRC5D, and a method for preparing the bispecific CAR-T cell. Specifically, the invention provides an autologous CAR-T cell which simultaneously aims at BCMA and GPRC5D antigen molecules and expresses a chimeric antigen receptor (CAR) in parallel. The invention also provides application of the CAR-T cell in adoptive T cell therapy of diseases such as multiple myeloma.

The invention relates to the field of cells, in particular to a composition for inducing autologous fibroblast reprogramming and application of the composition. According to the induction sequence, the composition comprises a first-stage small molecule compound, a second-stage small molecule compound and a third-stage protein molecule, and the first-stage small molecule compound is composed of Y27632, SAG, forskolin and Rapamycin; the second-stage small molecule compound is prepared from Y27632, SAG, forskolin, Rapamycin, AXL1717, RA and TNF-alpha (Tumor Necrosis Factor-alpha); the third-stage protein molecule is bFGF (basic fibroblast growth factor). The composition disclosed by the invention can be used for reprogramming fibroblasts so as to change the omics characteristics of the fibroblasts, so that the fibroblasts have enhanced immunoregulation, tissue repair and other biological functions related to treatment, and further safe, effective and unlimited autologous cell disease treatment is realized.

The WNT-ACTIVATED ADIPOSE-DERIVED STEM CELL APPARATUSES, METHODS AND SYSTEMS (hereinafter “WAADSC”) disclosed herein in various embodiments provide for production of an isolated and enriched population of mesenchymal stem cells that have an active Wnt signaling demonstrated by the elevated expression of Lgr5 marker and / or Nestin in more than 50% of the population. Such an autologous cell population may, in embodiments, be injected into cerebral ventricles of patients with neurodegenerative diseases to yield therapeutic results, such as halting the progression of certain conditions and / or ameliorating specific symptoms thereof.

The invention relates to the technical field of biomedicine, in particular to a biomarker for AML prognosis typing and application of the biomarker. Wherein the biomarker for the prognostic typing of the AML is a combination of a somatic mutation gene and an AML susceptible site genotype, the somatic mutation gene is selected from DNMT3A, and the AML susceptible site is selected from rs12459419. The combination of somatic mutation genes and AML susceptible site genotypes can further refine AML prognosis risk classification and improve the recognition ability of high-risk patients; meanwhile, prognosis typing of the AML is refined, research and development of specific drug targets for patients with different genotypes are facilitated, and then accurate treatment of the AML is achieved.

Methods, and compositions of matter useful for enhancing activity of endogenous and / or exogenous regenerative cells by selectively eliminating senescent cells through induction of immunity against said senescent cells or components thereof. Fusion of autologous patient cells made senescent, autologous antigen presenting cells and utilized as a vaccine. Autologous fibroblasts can be made senescent by genotoxic stress and fused with dendritic cells. Said dendritic cells may be generated from circulating monocytes, CD34 cells or autologous iPSC cells.

A cell mixture for the patient-specific treatment of solid tumors comprises carrier cells with a special loading. Immunocompetent autologous cells and / or genetically transfected cells are used, loaded with a combination of immunocompetent components and / or theranostic nanoparticles. The target tissue is derived from a tumor and includes malignant tumor cells and deactivated intratumoral cells, which are subsequently separated. Liposomes are loaded with a patient- and tumor-specific combination of immunocompetent components, namely at least one stable isotope with a high affinity for (epi-)thermal neutrons and / or a β- +The process involves the use of "decay" isotopes and / or a sensitizer to perform photodynamic therapy. Additionally, the cells are loaded with theranostic nanoparticles, which also allow for monitoring of the cells and charges involved. The carrier cells are gently loaded with the loaded liposomes via passive fusion. The loading rate of the carrier cells is significantly higher than with conventional methods, and at the same time, the carrier cells are highly specific to the individual tumor of the patient.

The application discloses a kind of acellular artificial lymph fluid drainage tube and its preparation method and application, the preparation method of acellular artificial lymph fluid drainage tube includes the following steps: with animal blood vessel as raw material, the raw material is treated, washing treatment, enhancement treatment, pore preparation treatment and drying treatment are carried out.This application preparation method is prepared to the acellular artificial lymph fluid drainage tube of preparation, can solve the problem that current lymphatic vessel-venous anastomosis operation is long, operation is difficult, can drain the lymph of patient swelling site to venous system in time after implantation, can quickly relieve swelling symptom.The acellular artificial lymph fluid drainage tube of the application supports the growth, migration, proliferation of autologous cells, and has good biocompatibility, the degradation time can be adjusted to match the reconstruction time of autologous lymphatic return system, to ensure long-term patency.