4109 results about "T cell" patented technology

The invention discloses a glioma T cell prediction and prognosis evaluation method based on pathological images, particularly relates to the field of patient prognosis health evaluation, and aims to solve the problems that existing pathological evaluation is difficult to combine with tumor structure heterogeneity and immune infiltration distribution, and the future progress risk of a patient cannot be predicted based on follow-up visit pathological data. A spatial heterogeneity map of a tumor core area and an invasion edge is constructed in a digital pathological section, density gradients of T cells in different areas are calculated to generate a distribution heterogeneity coefficient, interaction processing is performed on the two types of characteristics in combination with historical follow-up visit records, and a time sequence neural network constructed based on a gating structure is combined to obtain a high-efficiency characteristic of the tumor. And outputting disease progress probabilities of a plurality of follow-up visit time points in the future to form a prognosis trajectory prediction curve, calculating a quantitative recurrence risk score according to curve slope change and an immune fluctuation mode, and finally generating an individualized management scheme, thereby realizing quantitative prediction evaluation and risk management of the prognosis trend of the glioma patient.

The invention relates to the technical field of medical image analysis, in particular to a CAR-T cell culture monitoring system based on image recognition, which comprises a cell region division module, a cell morphology analysis module, a cell behavior dynamic analysis module and a cell population collaborative monitoring module. According to the method, through cell image gradient intensity analysis, refined cell edge detection and dynamic adjustment of a segmentation threshold value, high-precision extraction of cell boundaries is ensured, noise interference is avoided, cell shapes, textures and geometric features are refined, the identification degree of morphological features is improved, and tiny changes of cell morphologies are accurately captured; dynamic tracking and trend evaluation are carried out on cell behaviors based on adjacent frame images, tiny dynamic changes such as cell division, aggregation and migration are accurately reflected, excessive smoothness in the dynamic process is avoided, cell population behavior monitoring is combined with interaction and corresponding speed calculation, the population synergistic effect change trend is comprehensively evaluated, and the cell population behavior monitoring effect is improved. And finer cell culture environment optimization and clinical research support are provided.

The present invention provides a method for packaging a BaEV retroviral vector. The method includes constructing a stable BaEV retroviral packaging cell line, transfecting a retroviral vector plasmid containing a target sequence into a virus-producing cell line, where the virus-producing cell line is a HEK293T cell line or its derivative cell line, to harvest the transiently transfected and virus-producing retroviral vector, mixing it with the stable BaEV retroviral packaging cell line, and promoting the transduction of the retroviral vector into the stable BaEV retroviral packaging cell line by horizontal centrifugation. The present invention can achieve the packaging of a BAEV-type retroviral vector carrying a CD19CAR foreign gene plasmid, construct a BAEV-type retroviral vector-producing cell line, and produce a high-titer BAEV-type retroviral vector.

The invention discloses an attenuated salmonella typhimurium EN-VNP (Enhanced Natriuretic Peptide) strain as well as a preparation method and application of the attenuated salmonella typhimurium EN-VNP strain. Comprising the following steps: on the basis of a salmonella VNP20009 strain, flagellin genes fliC and fljB, a phosphoethanolamine transferase gene eptA, a 4-amino-4-deoxy-L-arabinose transferase gene arnT and phosphotransferase yeiU are sequentially knocked out or silenced, and a strain is formed after a phosphotransferase gene lpxE is knocked in or overexpressed, so that the attenuated salmonella typhimurium EN-VNP strain is prepared. According to the attenuated salmonella typhimurium EN-VNP with low toxicity and the T cell adjuvant effect and an EN-OMV antigen delivery system prepared from the attenuated salmonella typhimurium EN-VNP, an improved strain does not contain flagellin, an LPS molecular structure is changed, the attenuated salmonella typhimurium EN-VNP has the low toxicity and the T cell adjuvant effect, and normal multiplication culture can be achieved.

The invention discloses a nano system for tumor radioimmunotherapy and a preparation method and application thereof, and belongs to the technical field of biological medicines.The system modifies bacteria outer membrane vesicles (OMVs) through engineering to enable the bacteria outer membrane vesicles to carry magnetite nanoparticles (Fe3O4NPs) and an ATR inhibitor VE822, the Fenton reaction activity of the Fe3O4NPs and the synergistic effect of the ATR inhibitor for inhibiting DNA damage repair are utilized, and the tumor radioimmunotherapy effect is improved. DNA damage is amplified, DNA damage reaction (DDR) is inhibited, generation of hydroxyl radicals (. OH) under radiation is enhanced, radiation resistance of tumor cells is reduced, immune reaction is reactivated, infiltration of effector T cells to tumors is improved, growth of mice tumors is remarkably inhibited, and an effective strategy is provided for tumor radioimmunotherapy.

Disclosed herein are antibodies that specifically bind to Gal3 and methods of use thereof. In some embodiments, also described herein are methods of inducing immune activation or promoting T cell or Natural Killer cell proliferation with an antibody that specifically binds to Gal3. Also disclosed herein are methods and compositions of reducing fibrosis or propensity thereof in a tissue with antibodies that specifically bind to Gal3. In some cases, the anti-Gal3 antibody also disrupts the interaction between Gal3 and TIM-3.

The invention relates to the technical field of biological medicines, and particularly discloses an anti-human CD3 rabbit recombinant monoclonal antibody as well as a preparation method and application thereof. The antibody obtains anti-CD3 immune response by immunizing a rabbit, is obtained by combining single B cell sorting, gene cloning and a mammalian cell expression system, and has high affinity and good specificity. The antibody can effectively recognize CD3 positive T cells in human peripheral blood and can be applied to the fields of flow cytometry, immunohistochemistry, T cell function research and the like. Experimental results show that the antibody has the advantages of high titer, strong fluorescence signal, low background and the like, and is superior to the traditional murine anti-CD3 antibody. Amino acid sequences of light chain and heavy chain variable regions of the antibody are further obtained, and controllability and repeatability of antibody expression are achieved. The antibody has important scientific research value and industrial application prospect, and is suitable for various scenes such as T cell marker detection, immune state evaluation, immunotherapy auxiliary research and the like.

The present invention provides a combination of (i) an immune checkpoint modulator and (ii) a T-cell redirecting multifunctional antibody, or an antigen binding fragment thereof, for use in therapeutic treatment of a cancer disease. The T-cell redirecting multifunctional antibody comprises (a) a specificity against a T cell surface antigen; (b) a specificity against a cancer- and / or tumor-associated antigen; and (c) a binding site for human FcγRI, FcγRIIa and / or FcγRIII, wherein the antibody, or the antigen binding fragment thereof, binds with a higher affinity to human FcγRI, FcγRIIa and / or FcγRIII than to human FcγRIIb.

The present disclosure provides bispecific stealth lipid nanoparticle (LNP) compositions engineered to target specific tissues or cell-types, e.g., immune effector cells such as T cells, B cells, natural killer cells, and dendritic cells, to modify the cells with therapeutic nucleic acid encapsulated in the LNP. The present disclosure also provides compositions and methods of making the LNPs and treatment using the same.

The invention relates to the technical field of biological medicine, and discloses a pharmaceutical composition of paclitaxel dimer prodrug nanoparticles and a traditional Chinese medicine compound and application of the pharmaceutical composition, and the pharmaceutical composition is composed of Qiyuansanlong prescription freeze-dried powder and paclitaxel dimer prodrug nanoparticles; wherein the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) or GSH (glutathione) response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs), and the paclitaxel dimer prodrug nanoparticles comprise one of NQO1 response type PTX dimer prodrug nanoparticles (PTX-Q-PTX NPs) and GSH response type PTX dimer prodrug nanoparticles (PTX-SeSe-PTXNPs). According to the pharmaceutical composition disclosed by the invention, a traditional Chinese and western medicine synergistic treatment system is innovatively constructed, and the advantage of multi-dimensional synergistic interaction is shown. Firstly, an NQO1 / GSH double-response type intelligent release system is adopted, and a biomarker highly expressed by tumor tissue can be specifically responded to realize precise drug release, so that the PTX concentration in tumors is improved compared with that of a traditional dosage form, and meanwhile, the drug circulation time is prolonged. Secondly, the active ingredients in the Qiyuansanlong prescription freeze-dried powder can significantly down-regulate the PD-L1 expression level, synergistically enhance CD4 + T and CD8 + T cell infiltration, and form chemical-immune dual killing effects.

The present application relates to the field of biomedicine, and in particular to a tumor antigen peptide and a use thereof. Provided is a tumor antigen peptide, comprising a peptide segment having an amino acid sequence as shown in SEQ ID NO: 1. The provided tumor antigen peptide can be presented by the HLA subtype (HLA-A*11:01) having a high proportion of Chinese population. Additionally, by means of in vitro stimulation, the tumor antigen peptide is verified to effectively stimulate specific T cells, and a specific TCR element is successfully obtained. The present application lays a direct foundation for further developing TCR-T therapy targeting human TP53 R248Q and immunotherapy such as therapeutic vaccines.

The invention relates to an anti-CD3 nano antibody, an anti-CD38 antibody and a bispecific antibody containing the anti-CD3 nano antibody and the anti-CD38 antibody. According to the invention, an anti-CD3 nano antibody and an anti-CD38 monoclonal antibody are excavated and prepared, humanized design is carried out to obtain antibodies with high affinity and specificity, and different configurations of bispecific T cell conjugation antibodies targeting CD3 and CD38 are further designed, so that the CD3 and CD38 dual-specificity T cell conjugation antibodies are obtained. The antigen binding activity, the T cell-mediated tumor cell killing effect and the T cell proliferation and activation function of the antibody are systematically evaluated in vitro, and experimental results show that the T cell conjugation antibody can effectively recruit and activate T cells and has a remarkable killing effect on CD38 positive tumor cells, and it is further verified that the antibody has remarkable in-vivo anti-tumor activity and has a good application prospect. Therefore, the polypeptide has high affinity, good pharmacological characteristics and development potential.

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 discloses an application of CD4 + CD8 + double-positive T cells in improvement of poor immune reconstitution of HIV (human immunodeficiency virus) infected patients, and relates to the technical field of biological pharmacy, in particular to the application of preparation of the CD4 + CD8 + double-positive T cells in the poor immune reconstitution of the HIV infected patients. The number of peripheral blood CD4 + T cells of HIV infected patients is increased, the immune system of the patients is improved, and the probability of possible opportunity infection and other related diseases of the patients is reduced, so that the morbidity and mortality of the patients are reduced.

The invention discloses a lung adenocarcinoma prognosis risk prediction model and a construction method and application thereof, and belongs to the technical field of biomedical detection. The lung adenocarcinoma (LUAD) prognosis model is successfully constructed by systematically analyzing the immune infiltration related gene (CAFRG) of tumor-associated fibroblasts (CAF), and the application value of the lung adenocarcinoma (LUAD) prognosis model in prediction of patient prognosis is verified. The CAFRG risk score is negatively related to the immune microenvironment score and is remarkably related to immune checkpoint gene expression, which suggests that a high-risk patient may have the characteristic of immune escape. Furthermore, based on TIDE tool analysis, the patients in the low-risk group have more active T cell immune response. The risk score is also closely related to the sensitivity of antitumor drugs, especially Doramapimod. Therefore, a new theoretical basis is provided for personalized treatment of lung adenocarcinoma, and a new direction is provided for future clinical research.

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.

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 provides immune effector cells (for example, T cells, NK cells) that express a chimeric antigen receptor (CAR), and compositions and methods thereof.

Aspects described herein pertain to engineered chimeric antigen receptors (CARs) and compositions thereof having specificity and affinity for fluorescein containing ligands presented on the surface of tumor cells. Also provided herein are compositions including CARs further comprising a spacer arm and methods of making and using these compositions.

The invention provides a gamma delta T cell preparation as well as a preparation method and application thereof, and belongs to the technical field of T cells. The liposome is prepared from the following raw materials in parts by weight: 15-20 parts of modified gamma delta T cell liposome, 1-3 parts of cell stimulating factors and 4-7 parts of culture medium freeze-dried powder, the modified gamma delta T cell lipidosome is prepared by embedding gamma delta T cells through lipidosome, coupling with acetylenic bond modified chitosan, and further mixing with MFAP4 protein and b4GALT1 protein. The culture medium freeze-dried powder is prepared by freeze-drying the culture medium in the engineering culture process of gamma delta T cells, and the cell stimulating factors are resveratrol and quercitrin. According to the gamma delta T cell preparation prepared by the invention, the survival ability and resistance of gamma delta T cells are improved, the anti-tumor activity of the gamma delta T cells is improved, and the gamma delta T cell preparation has relatively good antioxidant and anti-inflammatory effects, reduces the inhibition of inflammation on an immune system and has a very good treatment effect on pancreatic ductal adenocarcinoma.

The invention belongs to the technical field of engineered probiotics, and particularly relates to engineered probiotics for radiosensitization and tumor metabolism regulation as well as a preparation method and application of the engineered probiotics. The engineering probiotics comprise probiotics and core-shell type metal nanoparticles which are loaded on the probiotics and are synthesized through a biological directional mineralization effect; the core of the core-shell type metal nanoparticle is a palladium element, and the outer layer of the core-shell type metal nanoparticle is a palladium element and a gold element. The engineering probiotics provided by the invention have excellent enzyme catalysis performance and can target and retain in tumor sites, and through the synergistic effect of all components in the engineering probiotics, adenosine metabolism is effectively inhibited, secretion of pro-inflammatory cytokines is enhanced, tumor microenvironment is promoted to be converted into an inflammatory state, up-regulation of immune checkpoints is inhibited, and the immune checkpoints are inhibited. And T cells are inhibited from being transformed into depletion phenotype and transformed into effect type from depletion type. After the SBRT and the immune checkpoint inhibitor are combined for use, the growth of tumors can be effectively inhibited, and the effect of enhancing immune radiotherapy is achieved.

The disclosure provides conjugates comprising a targeting moiety a lipid nanoparticle (LNP) encapsulating a therapeutic agent (e.g., payload) for delivery to immune cells. The conjugates can be delivered to immune cells ex vivo or formulated in a pharmaceutical composition and can be directly administered to a subject in need of (i.e., via in vivo administration).

Provided herein are methods and compositions for treating a subject having an autoimmune disorder, such as multiple sclerosis, autoimmune encephalitis, Sjogren's syndrome, kidney transplantation, IgG4-related disease, ANCA-associated vasculitis, chronic inflammatory demyelinating polyradiculoneuropathy, neuromyelitis optica spectrum disorder, and idiopathic inflammatory myopathy (e.g., antisynthetase syndrome, dermatomyositis, immune-mediated necrotizing myopathy, or polymyositis), using T cells engineered with a chimeric antigen receptor that binds CD19.

The present disclosure relates to T cells engineered to comprise a heterologous nucleic acid sequence encoding a dual mutant transforming growth factor beta 1 (dmTGFB1) under control of a promoter sequence and a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TGFBR2. In certain embodiments, the cells further comprise a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding a TNFA; a modification, e.g., knockdown, of an endogenous nucleic acid sequence encoding an IFNG; and insertion of sequence(s) encoding a regulatory T cell promoting molecule, and compositions and uses thereof.

The invention discloses a computer device and a computer readable storage medium for evaluating the immune reconstitution state of an HIV infected person after ART. Belongs to the field of computer information. The technical problem to be solved by the invention is how to evaluate the immune reconstruction state of an HIV infected person after ART. The invention provides a computer program stored in a memory in a computer device. The computer program comprises the following steps: S1, receiving sample data, namely the proportion of the number of cells expressing PD-1 in CD8 + T cells of peripheral blood mononuclear cells of an HIV infected subject after ART and the proportion of the number of cells expressing at least one of the following five factors: CD38, HLA-DR, CD57, PERFORIN and CD107A; s2, obtaining a predicted value Y from the sample data through a model formula, and outputting an immune reconstruction condition according to the predicted value Y and a pre-judgment condition; the method can accurately and efficiently determine whether the immune reconstruction state of the HIV infected person subjected to antiviral treatment is good or not.

The purpose of the present invention is to provide: a novel therapeutic or prophylactic agent for xerophthalmia; a therapeutic or prophylactic agent for graft-versus-host disease; a corneal epithelium wound healing promoter; a corneal invasive inflammatory cell inhibitor; or an inhibitor of differentiation of lymphocytes into effector T cells. The present invention provides: a therapeutic or prophylactic agent for xerophthalmia, a therapeutic or prophylactic agent for graft-versus-host disease, a corneal epithelial wound healing promoter, a corneal invasive inflammatory cell inhibitor, a tear amount maintenance agent, a corneal epithelial damage inhibitor, and a method for preparing the same, which comprises, as an active ingredient, a substance derived from a stem cell culture supernatant; a cell proliferation marker positive cell inhibitor, or an inhibitor of differentiation of lymphocytes to effector T cells.

In some aspects, the disclosure provides humanized immunodeficient mouse models that support long term transplantation and function of human T cells, natural killer cells, and bone marrow cells without the need for conditioning.

A bispecific antibody construct comprising a first human binding domain which binds to human CDH19 on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell. A nucleic acid comprising a polynucleotide encoding the antibody construct, a vector comprising the nucleic acid comprising the polynucleotide and a host cell transformed or transfected with the nucleic acid comprising the polynucleotide or vector. A process for the production of the antibody construct, a medical use of the antibody construct in the treatment of melanoma, and a kit comprising the antibody construct.

The invention relates to the technical field of biological medicine preparation equipment, and discloses an intelligent CAR-T cell culture system, which comprises an intelligent temperature control and cleaning box body, a double sterilization system and a full-automatic preparation process, and the intelligent temperature control and cleaning box body adopts temperature and humidity control and cleanliness control. The double sterilization system comprises hydrogen peroxide fumigation and ultraviolet circulation disinfection, and the full-automatic preparation process comprises a precise pipeline, a modular reaction unit and an automatic control platform. According to the intelligent CAR-T cell culture system, full-process automatic culture of full-automatic CAR-T cells is realized in a C-level environment, a high-requirement clean environment is not needed, the cost can be greatly reduced, the economic benefit is remarkable, a full-closed pipeline system better meets the requirements of laws and regulations, and the system has greater advantages in the supervision level; the full-automatic operation reduces the intervention of personnel, avoids the potential pollution risk in the process, the full-process automatic cultivation can greatly save the cost, and the cost is saved by 40% compared with the traditional process through comprehensive calculation.

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.