2065 results about "IMMUNOLOGIC CELLS" patented technology

The invention discloses a preparation method and application of a sea cucumber exosome with an immune cell repairing function, and belongs to the technical field of biomedicine. The method comprises the following steps: feeding sea cucumbers by using a combined method of composite stress and an echinacea extract, extracting sea cucumber cells, and obtaining sea cucumber exosomes through ultracentrifugation; wherein the condition of composite stress is set as follows: the day and night temperature difference is not lower than 3 DEG C, and meanwhile, the dissolved oxygen content of the water body is adjusted to 75-90% of the dissolved oxygen content of the conventional feeding water body. The obtained sea cucumber exosome has a remarkable immune cell repairing function, and can effectively promote proliferation and activity recovery of immune cells, inhibit expression of inflammatory factors and improve the level of anti-inflammatory factors. The sea cucumber exosome prepared by the preparation method disclosed by the invention has an important application prospect in the research and development of immune repair drugs, and can provide a technical support for a novel immune regulation preparation in the field of biomedicine.

The invention discloses a cord blood-derived regulatory T cell amplification culture medium and a use method thereof, and relates to the field of animal cell culture and immune cell therapy, the culture medium is a serum-free culture medium, the culture medium is composed of a basic culture medium, a serum substitute combination, a combination of four cell factors, an immunosuppressor, an apparent stabilizer and an antioxidant, and all the components play a role synergistically; according to the use method, cell amplification is realized through a collaborative process of staged environmental regulation and targeted activation. According to the method, the problems of exogenous pollution and batch difference caused by dependence of a serum-containing system on cord blood-derived regulatory T cell amplification in the prior art are solved, the defect that a serum-free scheme is difficult to consider the amplification efficiency and the function stability at the same time is overcome, the cell amplification quality and the clinical application safety are guaranteed, and the method is suitable for large-scale clinical transformation requirements.

The utility model relates to the technical field of cell cultivators, in particular to a pump-free perfusion micro-fluidic chip for multi-cell three-dimensional co-culture, which comprises a liquid storage layer, a liquid inlet and outlet layer, an upper channel layer, a lower channel layer and a packaging layer, realizes a one-way circulation perfusion dynamic co-culture system without a pumping system, reduces the occupied space of equipment, and is convenient to operate. Operation is simple, culture medium consumption is reduced, and cost is reduced; the separation of free NK cells and tumor infiltration NK cells is realized, and conditions are provided for researching molecular biological characteristics of different types of NK cells. The migration and interaction of the tumor spheres and the NK cells are observed in real time at the same time, so that the problem that a microfluid pump integrated by an external system is needed for separating free immune cells and tumor infiltration immune cells by existing equipment is solved.

Disclosed herein are an engineered immune cell with CD7 gene knock-out and use thereof. According to the present invention, an sgRNA specifically targeting CD7 gene is designed and synthesized, which can accurately target CD7 gene to achieve gene knock-out with high knock-out efficiency. The provided sgRNA can be used for preparing a CD7-targeting engineered immune cell, and can be further used for preparing a CD7-targeting universal CAR-T cell

The invention relates to the field of image analysis, in particular to a colon cancer lymph node metastasis risk prediction method and system based on image analysis. The method comprises the following steps: acquiring a pathological section scanning image, carrying out layer-by-layer downsampling and feature reconstruction, and generating pathological section topological features; carrying out adaptive clustering analysis and multi-parameter fusion evaluation on the basis of the pathological section topological features to obtain independent migration evaluation values of individual tumor cells; performing tumor metastasis branch analysis according to the independent migration evaluation value, and constructing a metastasis branch path distribution diagram; extracting an immunohistochemical staining image of a patient to obtain immune cell space distribution data; and performing multi-region lymphatic metastasis simulation and metastasis risk situation prediction based on the immune cell spatial distribution data and the metastasis branch path distribution diagram to obtain a final metastasis risk assessment result. According to the method, the lymph node metastasis risk is accurately and efficiently analyzed, and the credibility of a pathological analysis result is improved.

Provided herein are engineered immune cells and populations thereof for administration to patients to treat cancer (e.g., solid tumors or liquid tumors) and other conditions. The cells are engineered to functionally express a reduced level of one or more of RFX5, NLRC5, TAP2, β2m, TRAC, RFXAP, CIITA and RFXANK. The cells optionally are further engineered to express one or more than one additional protein such as an antigen binding protein (e.g., a chimeric antigen receptor (CAR) or T cell receptor) to target tumor cells or other damaged cells in the patient and / or to express other genes at a reduced level. Also provided are methods of making and using the engineered cells, compositions and kits comprising them, and methods of treating by administering the cells and the compositions.

Disclosed herein are antibodies or antigen-binding fragments thereof that specifically bind to human CD19. Chimeric antigen receptors and chimeric antigen receptor transgenes comprising an antigen binding domain that specifically binds to human CD19 are also disclosed. Also described herein are immune cells, viral vectors, and other compositions containing the antibodies, the antigen binding fragments, the chimeric antigen receptors, and / or the chimeric antigen receptor transgenes.

The invention belongs to the technical field of biological medicine, and relates to a composite polypeptide composition as well as a preparation method and application thereof. According to the technical scheme, pH responsive polymer loaded oligopeptide-1, acetyl heptapeptide-4 and palmitoyl tripeptide-1 are adopted as a core, hyaluronic acid is adopted for wrapping, a hyaluronic acid layer adsorbs palmitoyl tripeptide-8, heptapeptide-6 and decapeptide-4, and the composite polypeptide with a core-shell structure is prepared and used for treating inflammatory skin diseases. In the acute stage of inflammation, the active ingredients on the outer layer quickly inhibit the activation of proinflammatory factors and immune cells and relieve red, swollen and heat pain, and the gel outer layer formed by hyaluronic acid realizes continuous release, prolongs the action time and supplements moisture to the skin; the pH-responsive polymer of the inner layer releases active ingredients at the inflammation part, so that relapse is prevented, and the skin barrier function is repaired. The composition plays a role from multiple dimensions of inflammation regulation, barrier repair, oxidation resistance and the like through a multi-layer structure design and a multi-component synergistic effect.

Provided herein are chimeric cytokine receptors bearing a binding domain capable of binding a TGF-β ligand or a TGF-β receptor antibody. When present on chimeric antigen receptor (CAR)-bearing immune cells (CAR-T-cells), such receptors allow for increased CAR-T cell expansion, activity and persistence, constitutively and / or through engagement of a TGF-β ligand or a TGF-β receptor antibody. Also provided are methods of making and using the chimeric cytokine receptors described herein.

Provided for herein in several embodiments are immune cell-based (e.g., natural killer (NK) cell) compositions comprising CD19-directed chimeric antigen receptors. In some, embodiments the anti-CD19 binder portion of the CAR is humanized. In several embodiments, the humanized anti-CD19 CAR expressing cells exhibit enhanced expression of the CAR as well as enhanced cytotoxicity and / or persistence. Several embodiments include methods of using of the anti-CD19 CAR expressing immune cells in immunotherapy.

The invention belongs to the field of chemical medicines, and particularly relates to a combined medicine for preventing and / or treating prostatic cancer, application of the combined medicine and a medicine composition. The combined medicine disclosed by the invention comprises immune cells with enhanced infiltration degree and a galectin-1 inhibitor; the immune cells with enhanced infiltration degree are natural killer (NK) cells with TTTY15-USP9Y chimera RNA knocked out, the infiltration degree and anti-tumor activity of the NK cells in a prostate cancer microenvironment can be improved, and the activated NK cells have a stronger killing effect on tumor cells in vitro. The immune cells with enhanced infiltration degree and the galectin-1 inhibitor are combined for use, so that the composition shows a synergistic effect in treatment of prostatic cancer, and has a wide application prospect.

The present disclosure provides engineered immune cells modified to overexpress tumor sensing enhancer proteins, thereby providing the engineered immune cells with an enhanced ability to migrate to and / or infiltrate tumors. In some examples, the tumor sensing enhancer proteins are tumor sensing receptors that specifically bind to non-chemokine receptors. The disclosure also provides methods including the provided engineered immune cells.

The present invention relates to an antibody or an antigen-binding fragment thereof binding to CLDN18.2, an antibody-drug conjugate comprising same, and a use of the antibody and the antibody-drug conjugate. An anti-CLDN18.2 monoclonal antibody according to the present invention comprises a fully human antibody sequence, thereby having low in vivo immunogenicity, and exhibits excellent antigen affinity and binding ability specific to a low expression to a high expression level of the CLDN18.2 protein. Thus, the antibody is expected to exhibit high specificity and safety as an antibody-based therapeutic agent such as in the form of a monoclonal antibody and / or an antigen-binding fragment (scFv), an antibody-drug conjugate (ADC), an immune cell engager, a chimeric antigen receptor (CAR), a multispecific antibody, and the like. In addition, the antibody according to the present invention may undergo cellular internalization, enables an anti-CLDN18.2 antibody-drug conjugate comprising said antibodies to be conveniently prepared, and has excellent yield and quality and thus is expected to be highly likely to be developed as a drug. A drug conjugate comprising the anti-CLDN18.2 antibody according to the present invention has excellent in vivo anticancer efficacy and has an expanded therapeutic index (TI) and thus is expected to be usefully employable for the treatment and / or prevention of cancer diseases expressing CLDN18.2 and related diseases.

The present invention relates to antibody-cytokine conjugates, wherein the cytokine is conjugated to the antibody via a cleavable linker. Conjugates according to the invention can be prepared by coupling a functionalized antibody Ab (F) x comprising x reactive moieties F, where x is an integer in the range of 1-10, with an immune cell-binding polypeptide comprising one or two reactive moieties Q, where the antibody is specific for tumor cells, and the immune cell-binding polypeptide is specific for immune cells, wherein the reaction forms a covalent bond between the functionalized antibody and the immune cell-binding polypeptide by reaction of Q with F. The invention further relates to antibody-cytokine conjugates obtainable by the method according to the invention and to medical uses thereof.

Genetically engineered immune cells, which express at least two metabolism modulating polypeptides and optionally a chimeric receptor polypeptide (e.g., an antibody-coupled T cell receptor (ACTR) polypeptide or a chimeric antigen receptor (CAR) polypeptide) capable of binding to a target antigen of interest. Also disclosed herein are uses of the engineered immune cells for inhibiting cells expressing a target antigen in a subject in need thereof.

The invention discloses an auxiliary diagnosis system for renal transplantation rejection and typing thereof based on a peripheral blood immune cell map. Comprising a peripheral blood single cell acquisition unit, a mass spectrum flow cytometry unit, an original data preprocessing unit, a data conversion and normalization processing unit, a peripheral blood immune cell grouping acquisition unit, a peripheral blood immune cell map construction unit, a feature vector acquisition unit, a rejection prediction unit and a rejection typing prediction unit. According to the invention, a kidney transplantation two-stage diagnosis architecture is created for the first time; rejection detection and typing identification are realized through classification of an independently trained random forest binary classifier, and different TCMR / ABMR immune mechanisms are accurately matched; the traditional biopsy limitation is broken through, an auxiliary diagnosis scheme with high precision, low damage, moderate cost and typing identification capability is provided for the kidney transplantation rejection, and the method has important significance on timely discovery of the rejection of a kidney transplantation patient and improvement of prognosis.

The invention relates to the field of immunology, and particularly discloses a hepatitis B virus specific TCR combination and application, the hepatitis B virus specific TCR combination is used for recognizing HBV antigen epitopes, the hepatitis B virus specific TCR combination comprises a plurality of separated TCRs, the plurality of separated TCRs form two TCR groups, and the two TCR groups comprise a first TCR group and a second TCR group; wherein the first TCR group specifically recognizes a first antigen epitope, and the amino acid sequence of the first antigen epitope is as shown in SEQ ID NO: 1; the first TCR group specifically recognizes a first antigen epitope, the second TCR group specifically recognizes a second antigen epitope, the amino acid sequence of the second antigen epitope is shown as SEQ ID NO: 2, the second antigen epitope respectively and correspondingly recognizes different antigen epitopes, the hepatitis B virus specific TCR and the epitope thereof are screened out, and an important means can be provided for treatment of TCR-T immune cells infected by hepatitis B virus.

The present application belongs to the technical field of medicine, and particularly relates to the use of tetrahydrojatrorrhizine or a pharmaceutically acceptable salt thereof in the preparation of a medicament for treating rheumatoid arthritis. Experimental results show that tetrahydrojatrorrhizine can effectively alleviate the foot swelling level of CIA rats, reduce the arthritis score, and inhibit the progression of rheumatoid arthritis. Blood routine analysis shows that the administration of tetrahydrojatrorrhizine reduces the number of immune cells in the blood and weakens the immune level of the body. In addition, the experimental results also show that tetrahydrojatrorrhizine can inhibit synovial hyperplasia and relieve joint damage. Therefore, tetrahydrojatrorrhizine has the prospect of being developed into an oral medicament for treating rheumatoid arthritis, provides more treatment options for clinically treating rheumatoid arthritis, and has important social and economic values.

An antigen-binding molecule capable of binding to multiple different antigens (e.g., CD3 on T cells, and CD137 on T cells, NK cells, DC cells, and / or the like), but does not nonspecifically crosslink two or more immune cells such as T cells is provided. Such multispecific antigen-binding molecule is capable of modulating and / or activating an immune response while circumventing the cross-linking between different cells (e.g., different T cells) resulting from the binding of a conventional multispecific antigen-binding molecule to antigens expressed on the different cells, which is considered to be responsible for adverse reactions when the multispecific antigen-binding molecule is used as a drug.

A chimeric autoantibody receptor (CAAR) that enables targeting of an immune cell to autoantibody producing B cells. The CAAR includes an autoantigen or fragment thereof that is bound by autoantibodies associated with neurological autoimmune disease primarily targeting the central nervous system. Also disclosed is a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), the nucleic acid sequence encoding an autoantigen or fragment thereof that is bound by autoantibodies associated with a neurological autoimmune disease primarily targeting the central nervous system, a transmembrane domain, and an intracellular signaling domain, a vector comprising a nucleic acid molecule encoding a chimeric autoantibody receptor (CAAR), a genetically modified immune cell comprising the nucleic acid molecule encoding the CAAR and use of the immune cell in the treatment or prevention of a neurological autoimmune disease primarily targeting the central nervous system, such as an autoimmune encephalopathy or encephalomyelopathy, preferably anti-NMDAR encephalitis.

The invention relates to the technical field of biomedicine, in particular to a liver cancer molecular subtype typing and prognosis model construction method based on glycometabolism and lactic acid metabolism related genes and application thereof. According to the invention, the typing and prognosis model of liver cancer subtypes is constructed for the first time on the basis of a coordinated regulation network of a glycometabolism gene and a lactic acid metabolism gene, the constructed liver cancer subtype subtypes comprise Cluster1 and Cluster2, and the total survival rates of different subtypes have significant difference; the clinical characteristics T.stage and TNM.stage of different subtypes are obviously different from each other; 12 kinds of immune cells have significant differences among different subtypes; iPS immune scores of different subtypes are significantly different; the TIDE scores of different subtypes have significant score differences; the genes with the highest mutation frequency in different subtypes comprise TP53, CTNNB1 and TTN. CLM scores of the prognosis model constructed on the basis of the collaborative regulation network of the glycometabolism genes and the lactic acid metabolism genes have no significant difference in different patient states; the 17 immune cells have significant differences between high and low risk groups. And a new way is provided for individualized treatment strategy formulation and survival outcome improvement of HCC.

The invention provides an ultrahigh-energy immune cell, the content of NAD < + > in the ultrahigh-energy immune cell is more than two times that of immune cells in a human body, and / or the number of mitochondria in the ultrahigh-energy immune cell is more than 1.1 times that of mitochondria in the immune cells in the human body. The invention also provides a preparation method of the ultrahigh-energy immune cell, and the immune cell is cultured through an NAD + reduced precursor.

The present disclosure relates to proteomics, including the detection of immune cell target proteins as examples that the disclosed methods can be used for protein detection. Methods, compositions, and systems are described for identifying the presence of proteins, including detecting immune cell proteins from a sample using a combination of multiplex immuno-PCR with antibodies conjugated to oligonucleotides comprising an antibody-specific barcode flanked by PCR priming sites; detection of barcoded amplicons obtained from immuno-PCR with encoded padlock probes comprising codes specific for the barcodes / target protein; rolling circle amplification (RCA) of the circularized padlock probes; and determination of the sequence of the codes amplified by RCA by next generation sequencing or using fluorescently labeled hybridization probes.

Provided herein is a DNA analysis method for detecting and quantifying immune cell types from which the DNA originated. Provided herein are also methods for determining the likelihood that a subject has a disease or condition, such as cancer.

Several embodiments disclosed herein relate to methods and compositions for enhanced expansion of NK cells in culture, through the repeated co-culturing of NK cells with feeder cells and the selective use of stimulatory interleukins. In several embodiments, the methods utilize one or more soluble interleukins as culture media supplements at one or more time points during expansion of the NK cell, or other immune cell, which results in a highly expanded and highly cytotoxic population of cells, for use in, for example allogeneic cellular immunotherapy.

Described herein are methods, systems, and programming for determining a tumor immunophenotype of an image of a tumor. Some embodiments include dividing an image into tiles depicting tumor epithelium and / or tumor stroma. For each tile, an epithelium-immune cell density and a stroma-immune cell density may be calculated based on a number of immune cells identified in the tumor epithelium and the tumor stroma, respectively. Based on the epithelium-immune cell density and the stroma-immune cell density, an inflammation type of the type may be determined, and a tumor immunophenotype may be determined based on each tile's inflammation type.

The present invention relates to: a receptor tyrosine kinase like orphan receptor 1 (ROR 1) antibody or an antigen-binding fragment thereof; a nucleic acid encoding same; a recombinant expression vector carrying the nucleic acid; a host cell transinfected with the recombinant expression vector; a method for preparing the antibody or the antigen-binding fragment thereof; a bi- or multi-specific antibody bearing the antibody or the antigen-binding fragment thereof; an immune cell-engaging bi- or multi-specific antibody; an antibody-drug conjugate (ADC) in which the antibody or the antigen-binding fragment thereof is bound to a drug; a chimeric antigen receptor (CAR) containing the scFv of the antibody as an antigen-binding site of an extracellular domain; an immune cell having the chimeric antigen receptor introduced thereinto; a composition for combination therapy including the antibody or the antigen-binding fragment thereof; a composition for preventing or treating cancer; and a method for preventing or treating cancer.

Disclosed herein are immune cells expressing engineered cytokine receptor switches which, upon activation, can direct differentiation of the immune cells. The present disclosure further provides compositions and methods for transfecting, expanding, and activating these immune cells, including substrates which activate the engineered cytokine receptor switches disclosed herein.

The invention relates to an STING gene knockout TIL capable of enhancing anti-tumor activity and a preparation method and application of the TIL, in particular to a genetically engineered immune cell, and an STING gene in the genetically engineered immune cell is silenced or down-regulated. The ferroptosis resistance of the immune cell provided by the invention is remarkably enhanced, the immune cell can be better infiltrated into a tumor microenvironment, and the immune cell has a remarkable anti-tumor effect.

Relates to a modified delivery carrier and application thereof. The modified delivery carrier comprises a delivery carrier and a targeting domain coupled with the delivery carrier, the delivery carrier is used for loading a reagent, and the targeting domain can specifically target a surface antigen of an immune cell.