35 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 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.

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 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.

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.

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 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.

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.

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

The application discloses a gp96 tumor neoantigen prediction method and application thereof, and relates to the technical field of tumor neoantigen prediction. The method comprises the following steps: S1, isolation and purification of gp96-tumor polypeptide complexes; S2, dissociation and purification of polypeptides; S3, mass spectrometric identification and sequence analysis of mutant peptides; S4, MHC affinity prediction; and S5, immunogenicity verification. The application takes gp96 as a natural biological concentrator, the captured polypeptides include products in a natural antigen processing path of tumor cells, and antigen peptide segments with potential immunological significance are enriched. In combination with MHC affinity prediction and immunogenicity function verification, the true positive rate of neoantigen screening is significantly improved. In a verification experiment on colon cancer samples, among 7 candidate neoantigens obtained through prediction, 4 can significantly activate autologous T cells of a patient to secrete IFN-gamma, and show a high immunogenicity verification positive rate.

An isolated trifunctional bispecific antibody for use in a method of treating a patient suffering from a disease and / or disorder associated with reactivation of Epstein-Barr virus (EBV) in at least B cells and potentially other susceptible cells, such as susceptible epithelial cells, the method comprising: providing an autologous cell preparation of enriched B cells of the patient; incubating the enriched B cells with a trifunctional bispecific antibody for a period of time sufficient to establish a physical interaction between the trifunctional bispecific antibody and the enriched B cells to obtain an incubation mixture; transferring the incubation mixture obtained after incubation into the same patient, wherein the trifunctional bispecific antibody comprises: (a) a first binding arm binding to B cells via a B cell surface antigen; (b) a second binding arm binding to T cells via a T cell surface antigen; (c) an Fc part binding to Fc receptor positive cells. The invention also discloses a pharmaceutical composition comprising the isolated trifunctional bispecific antibody for use in treating a patient suffering from a disease and / or disorder associated with reactivation of EBV in B cells, and an ex vivo method for the preparation of the pharmaceutical composition.

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.

This disclosure relates to a tumor immunotherapy composition, preparation method, and application based on specific immune cells, particularly specific immune cells activated by attenuated Listeria monocytogenes carrying non-integrating antigenic peptide plasmids. The disclosure involves extracting T cells in vitro, co-culturing T cells with antigen-presenting cells activated by attenuated Listeria monocytogenes, and generating T cells with specific tumor antigenic peptides in vitro. These specific T cells are then reinfused into the body to generate a tumor-specific immune response. The technical solution of this disclosure can specifically activate tumor-specific T cells, thereby triggering a series of anti-tumor immune responses. Furthermore, the process does not require genetic modification of autologous cells, significantly improving both targeting and safety.

The invention provides a therapeutic cell as well as a preparation method and application thereof, a T cell and an NK cell can be combined for use by constructing a chimeric antigen recipient cell for secreting a bispecific immune cell adapter, and T / NK cell combined redirection is realized to treat tumors. Compared with various single immune cell redirection therapies, the method has the advantages that the dependence on the number of autologous T cells is reduced while the excellent anti-tumor efficacy is achieved, the defects that the lifetime of NK cells is short and the half-life period of a bispecific antibody is short are overcome, the histocompatibility and safety are improved, and the application prospect is wide. In addition, the immune escape problem caused by tumor antigen deletion and mutation can be better solved, and clinical requirements are met.

CD38 is also expressed in a variety of malignant hematological diseases, including multiple myeloma. In the present invention, the inventors have generated a new antibody against CD38 that could be suitable for producing bispecific antibodies as well as CAR-T cells. In particular, the inventors report the development of Bi38-3, a new bispecific T cell engager that targeted CD38 on MM cells and recruited cytotoxic T cells through the CD3ε. Bi38-3 lacked the Fc region of natural mAb, which contributes to resistance processes, but triggered T cells to proliferate, release cytokine and lyse CD38 positive MM cells in vitro. Similarly, Bi38-3 induced autologous T cells to eliminate tumor plasma cells isolated from MM patients both at diagnosis and at relapse. The cytotoxicity triggered by Bi38-3 was restricted to cells expressing high levels of CD38 and preserved the integrity of T, B and NK lymphocytes in vitro. Importantly, Bi38-3 rapidly reduced tumor cells in an MM1.S xenograft mouse model of human MM. Taken together, the results show that the antibody of the present invention is an effective reagent to specifically eliminate CD38 positive malignant cells without significantly affecting CD38 lowly expressing cells and represents a promising novel immunotherapeutic tool for the treatment of malignant hematological diseases, and especially multiple myeloma.

Disclosed are bispecific single-chain constructs that bind to both C-type lectin-like molecule-1 (CLL-1, also known as CLEC12A) and CD3, pharmaceutical compositions comprising the constructs, methods of treatment using the pharmaceutical compositions, polynucleotides encoding the constructs, and methods of making the constructs. The disclosed methods include contacting cells, e.g., autologous T cells, with the disclosed constructs ex vivo and administering the contacted cells to a subject.

The invention discloses a method for amplifying Treg cells and a Treg cell culture medium. The method for amplifying the Treg cells comprises the following steps: extracting PBMC (peripheral blood mononuclear cells) from autologous plasma; carrying out magnetic bead sorting on CD4 + T cells in the PBMC; the cell suspension is resuspended in a Treg cell culture medium, culture is conducted, cells are collected after 14 days, and a Treg amplification culture medium comprises 5% thermally inactivated autologous plasma, glutamine, HEPES, beta-ME, Rapamycin, Decitabine, IL-2 and alphaCD3 / CD28. According to the invention, CD4 + T cells can be efficiently induced to generate Treg cells, and the obtained autologous Treg cells can be applied to various autoimmune diseases and other clinical demand conditions for inducing peripheral immune tolerance.

The invention discloses an autologous cell regulation system and method for improving human body interstitial fluid circulation aiming at chronic diseases, and aims to solve the regulation problem related to chronic diseases and circulation metabolism abnormality. According to the scheme, the method comprises the following steps: drawing 80m l of venous blood of a subject, dividing into eight tubes, putting into a cell preparation device, and separating out a protein factor layer, a seedless cell layer and a red blood cell layer; the first two layers are collected and subjected to liquid nitrogen lysis for five times (freezing for 5 minutes and unfreezing for 20 minutes per cycle) to prepare an autologous cell lysis solution which is used for venous transfusion or organ / site targeted injection, and a red blood cell layer is transfused back into a body. Interstitial fluid circulation is improved through the lysate, whole body metabolism is optimized to regulate chronic diseases, the advantages of being free of autologous rejection, minimally invasive and high in resource utilization rate are achieved, and a new path is provided for treatment of the chronic diseases.