710 results about "Natural Killer Cell Inhibitory Receptors" patented technology

The invention discloses preparation of a whey protein peptide mixture with immune and muscle-building effects, and relates to the technical field of food processing and bioengineering. The neutral protease is adopted and the pH is adjusted, so that the enzymolysis efficiency is effectively improved, and the enzymolysis time is greatly shortened; meanwhile, the whey protein peptide which is uniform in molecular weight distribution, free of peculiar smell and good in thermal stability is successfully prepared by accurately controlling enzymolysis conditions and combining microbial fermentation. The protein peptide can effectively improve thymus indexes and spleen indexes, enhance the proliferation capacity of splenic lymphocytes and the activity of NK cells, play an excellent immune regulation role and have a remarkable muscle building effect. The preparation process has the advantages of high efficiency, low cost, simplicity, convenience and the like, gives consideration to high quality and high functionality of the product, and has great application value.

The invention relates to the field of image processors and biological medicines, and discloses an NK cell activity rapid detection method based on image processing. The method comprises the following steps: acquiring an unmarked time sequence phase image sequence of an NK cell and target cell co-culture system; performing cell instance segmentation to track individual cells; extracting a morphological dynamic characteristic parameter set of the target cell, wherein the morphological dynamic characteristic parameter set comprises a volume change rate, a phase gradient entropy, a cytoplasm phase fluctuation frequency and a nuclear region phase mean value; inputting the parameters into a pre-trained death state discrimination model, and outputting a death probability; and calculating a killing efficiency index based on the death probability evolution curve, and judging the activity level of the NK cells. The system comprises a phase image acquisition unit, a cell segmentation unit, a feature extraction unit, a death judgment unit and an activity judgment unit. Through unmarked imaging and deep learning fusion analysis, high-precision, real-time, quantitative and ultra-early NK cell activity evaluation is realized, and the method is suitable for clinical instant inspection and immunotherapy monitoring.

The invention provides application of a substance for detecting the ratio of lymphocyte subgroups in preparation of a reagent or a kit for diagnosis or auxiliary diagnosis of Graves disease, and belongs to the technical field of preparation of disease diagnosis reagents. A research shows that compared with a healthy sample, the proportion of B cells in a lymphocyte subpopulation of a to-be-detected sample is remarkably increased, the proportion of NK cells is remarkably reduced, the proportion of activated T cells is remarkably reduced, the proportion of memory T cells is remarkably reduced, the proportion of CD4 + memory T cells is remarkably reduced, the proportion of Th1 cells is remarkably reduced, and the proportion of Tc1 cells is remarkably reduced, so that the to-be-detected sample is a GD patient; the substance for detecting the ratio of lymphocyte subgroups is high in sensitivity and specificity when being used for diagnosis or auxiliary diagnosis of Graves disease.

The invention discloses a fusion protein of a bispecific antibody targeting a T cell and Her2 in series connection with IL-15 and a receptor thereof and an application of the fusion protein. Belongs to the technical field of biology. The fusion protein disclosed by the invention can be combined with a recombinant human CD3 protein and a recombinant human Her2 protein, can be combined with NK92 and SK-BR-3 cell lines, can stimulate NK92 cell proliferation, and can respectively cause ADCC effects mediated by T and NK cells; the antibody has important economic and social significance.

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.

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.

The invention provides compositions and methods for treating diseases associated with expression of CD20 or CD22. The invention also relates to chimeric antigen receptor (CAR) specific to CD20 or CD22, vectors encoding the same, and recombinant T or natural killer (NK) cells comprising the CD20 CAR or CD22 CAR. The invention also includes methods of administering a genetically modified T cell or NK cell expressing a CAR that comprises a CD20 or CD22 binding domain.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

The invention relates to an immune sensitization IRE treatment platform based on NK cell membrane coated manganese carbonate. A manganese carbonate composite nano material is formed by coating the surfaces of manganese carbonate nano particles with cell membranes. According to the invention, higher tumor specificity enrichment is realized, non-target tissue accumulation and systemic toxicity risks are reduced, collaborative integration of tumor targeted delivery, immune activation and IRE ablation is realized, and compared with single IRE, anti-tumor immune response is significantly enhanced.

The invention relates to an antibody composition for detecting abnormal CTL (cytotoxic T lymphocyte) cells of hemophagocytic syndrome and application of the antibody composition, and the antibody composition comprises a CD2 antibody, a CD3 antibody, a CD4 antibody, a CD5 antibody, a CD7 antibody, a CD8 antibody, a CD56 antibody, a CD57 antibody, a Granzyme B antibody, a Perforin antibody, a TRBC1 antibody and a CD45 antibody. In the technical scheme provided by the invention, key phenotypic characteristics of CTL (Cytotoxic Lymphocyte) can be completely covered by various antibodies aiming at T cell and NK cell surface markers, T large granular lymphocyte markers, cytotoxic granular proteins, T cell receptor constant regions and leukocyte common antigens; wherein the clonality of the CTL cells is judged through the expression level of the TRBC1 antibody, and the cytotoxic function activity of the CTL cells is evaluated through the expression levels of Granzyme B and Perforin.

Provided herein are compositions of NK-92™ cells that express a combination of PD-L1 CAR, CD16 and IL2, and the method of using these cells to to reduce tumor cells and cells in tumor microenvironment (e.g., MDSCs or TAMs) and treat cancer.

The present disclosure features modified immune effector cells (e.g., T cells or NK cells) having increased resistance to inhibition of an immunosuppressive agent relative to unmodified immune effector cells, compositions comprising the same, and methods of using the same.

The invention discloses a culture method for improving proliferation and differentiation capacity of NK (Natural Killer) cells based on angelica sinensis-astragalus membranaceus exosomes, which comprises the following steps: firstly extracting exosomes in angelica sinensis and astragalus membranaceus, then adding the exosomes into an NK cell culture system according to a specific concentration, and regulating and controlling an NK cell signal channel by virtue of active ingredients carried by the exosomes so as to improve the proliferation and differentiation capacity of the NK cells. Therefore, the proliferation rate and differentiation maturity of the NK cells are remarkably improved. Experimental results show that compared with a traditional culture method, the proliferation multiple of the NK cells cultured through the method is increased by 28.99%-33.69%, the proportion of differentiated mature cells is increased by 15.91%-28.30%, and the cell killing activity is not remarkably reduced. The method can be widely applied to the field of immune cell treatment, provides a high-quality NK cell source for clinic, effectively solves the problems of slow cell proliferation rate, low differentiation maturity, easy activity reduction after large-scale culture and the like in traditional NK cell in-vitro culture, and has important clinical application value and industrialization prospect.

The invention relates to the technical field of novel biological nanomaterials, in particular to a lung-targeted exosome complex as well as a preparation method and application thereof. The lung targeting type exosome complex is prepared from an NK cell exosome, lipid nanoparticles and an entrapped anti-tumor nucleic acid drug, the NK cell exosome is obtained by extracting a natural killer cell NK-92MI of a human malignant non-Hodgkin lymphoma patient through a differential centrifugation method. The anti-tumor nucleic acid drug is a specific nucleic acid drug targeting a key canceration driving gene in non-small cell lung cancer. The lung targeting type exosome complex prepared by the invention is an excellent and stable drug delivery carrier, has a good lung tissue targeting function, enhances the tumor targeting effect of the exosome, also exerts the tumor cell killing function of the exosome, and has important significance for the treatment of non-small cell lung cancer.

The invention discloses an NK cell culture solution and an NK cell culture. The culture solution comprises a cell activation culture solution and a cell amplification culture solution, the cell activation culture solution comprises a basic culture medium, and the basic culture medium contains autologous plasma with the final concentration of 1-10%, IL-2 with the final concentration of 50-1000U / mL, IL-15 with the final concentration of 1-15ng / mL, OK432 with the final concentration of 0.1-1ug / mL and ginseng exosome with the final concentration of 1-10ug / mL; the cell amplification culture solution comprises a basic culture medium, and the basic culture medium contains IL-2 with the final concentration of 100-2000U / mL. The ginseng exosome component in the cell culture fluid can promote NK cell proliferation and remarkably improve the immune killing function of the NK cells, and the ginseng exosome serving as an activating factor can effectively improve the activity of the NK cells and enhance the immune effect of the NK cells.

The present invention relates generally to the use of LSD1 inhibitors in connection with use and manufacture of immune effector cells (e.g., T cells, NK cells), e.g., engineered to express a chimeric antigen receptor (CAR), to treat a subject having a disease, e.g., a disease associated with expression of a tumor antigen.

Several embodiments of the methods and compositions disclosed herein relate to immune cells that are engineered to express chimeric antigen receptors as well as genetically edited or otherwise engineered enhance the persistence the cells in immunotherapy. In several embodiments, the cells are edited to knock out a target gene that encodes a protein involved in antigen processing and presentation by major histocompatibility complex class I molecules. In several embodiments, a mixture of immune cell types is used, optionally in allogeneic therapy. The engineering and editing of the cells, such as NK cells and / or T cells exhibit enhanced cytotoxicity and / or persistence, as well as reduced risk of reduced graft versus host, host versus graft, and graft versus graft effects.

Provided herein are methods for pre-activating and expanding an isolated population of NK cells. Further provided herein are methods for the treatment of cancer by administering the pre-activated and expanded NK cells.

The invention provides an immortalized NK cell line SZ093 derived from healthy human umbilical cord blood as well as a preparation method and application of the immortalized NK cell line SZ093. The immortalized NK cell line SZ093 derived from the healthy human umbilical cord blood is preserved in Guangdong Microbial Culture Collection Center on September 26, 2025, and the preservation number is GDMCC No: 67036. The immortalized NK cell line SZ093 derived from the healthy human umbilical cord blood, provided by the invention, can still keep good multiplication capacity and high survival rate in a long-time (more than one year) culture process, and has high killing capacity on tumor cells.

The invention relates to the field of biology, in particular to a preparation method of NK cells and application of the NK cells in cancer treatment. The method is an antibody-cell therapy, the persistence and killing efficiency of the NK cells are further improved through a targeted antibody, and wide clinical application prospects are shown.

The present application relates to the field of immunology, and particularly relates to a novel IL-15 fusion protein and application thereof. The present application provides an IL-15 transmembrane fusion protein, which is applied to NK cells or CAR-NK cells, can significantly enhance the tumor killing function of NK cells and CAR-NK cells, and can effectively promote the proliferation of NK cells and CAR-NK cells. It provides an important basis for developing NK cell products armored by the IL-15 transmembrane fusion protein, which are independent of any tumor target, thereby reducing the cycle and cost of CAR-NK development. Meanwhile, the present application respectively carries out function research in blood tumors expressing CD19 and solid tumors expressing CD276, and the results indicate the broad-spectrum application prospect of the structure in tumors.

The invention belongs to the technical field of biological genetic engineering, and particularly relates to a mouse model construction scheme capable of reproducing a key phenotype of hemophagocytic syndrome, which comprises the following steps: inserting a loxP-STOP-loxP-LMP1 conditional expression cassette into a Rosa26 safe port site in a fixed point manner to obtain an Lmp1cKI mouse strain; and hybridizing the mouse with an Ncr1-Cre transgenic mouse of NK cell specific expression Cre recombinase. In a double transgenic offspring (Lmp1Ncr1-Cre), STOP fragments are cut off by Cre enzyme, and continuous high expression of EB virus LMP1 protein in NK cells is driven. The model does not need chemical induction or immune intervention, and typical hemophagocytic syndrome phenotypes, namely serum IL-6, TNF-alpha and IFN-gamma, spontaneously appear within 7-9 days after young rats are born; the body weight is reduced and the survival rate is obviously reduced; the proportion of lymphocytes is sharply reduced; and NK cells are depleted. The invention provides a stable and reliable tool for hemophagocytic syndrome pathogenesis research, drug screening and treatment evaluation.

The invention discloses a method for culturing NK (Natural Killer) cells. The method comprises the following steps: inoculating a mononuclear cell into a T25 cell culture flask, wherein the T25 cell culture flask is coated by a coating factor in advance; carrying out culture treatment on the inoculated mononuclear cells in a culture system containing an NK cell culture medium containing an activation amplification factor and plasma so as to obtain NK cells; wherein the coating factor, the activation amplification factor and the NK cell culture medium are derived from an NK cell amplification kit. According to the method provided by the embodiment of the invention, the dosage of the amplification reagent can be reduced, the amplification multiple of the NK cells is improved, and the production cost is reduced.

The invention discloses a method for establishing a hemophagocytic syndrome in-vitro cell disease model, and belongs to the technical field of biology. Based on human PBMC construction, the reaction of a human immune system can be truly reflected, experimental result deviation caused by species difference in an animal model is avoided, and a more accurate model basis is provided for research of human diseases. In addition to T cell over-activation, the HLH model of the present application has a clear key feature of NK cell reduction, which is HLH, accompanied by up-regulation of cytokines such as interferon-gamma and IL-10. The establishment process of the model is rapid and efficient, the experimental period is remarkably shortened, a large number of samples or drugs can be rapidly screened, the research efficiency is improved, and the conversion process from basic research to clinical application is accelerated. The method can be used for researching various mechanisms related to the HLH, is beneficial to more comprehensive understanding of pathogenesis of the HLH, and provides a theoretical basis for developing preliminary screening of targeted drugs.

This invention provides engineered natural killer (NK) cells and methods for producing engineered NK cells. [Solution] The present invention provides engineered natural killer (NK) cells, which are genetically modified to reduce the expression, activity, and / or signaling of the FcRγ chain in the cells. The engineered NK cells and compositions comprising the engineered NK cells are useful for treating diseases such as cancer.

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

Abstract Described herein, in one aspect, are antigen presenting cells (APCs) comprising an exogenous nucleic acid encoding one or more candidate antigens, wherein the one or more candidate antigens are expressed and presented with MHC class I or MC class II molecules; a molecular reporter of Granzyme B (GzB) activity; and c) an exogenous inhibitor of caspase-activated deoxyribonuclease (CAD)-mediated DNA degradation, a CAD knockout, or a caspase knockout (e.g., caspase 3 knockout). Described herein, in another aspect, is a system for detection of recognized antigen presentation by an antigen presenting cell to a cytotoxic lymphocyte or NK cell. Abstract 2018 / 22761 oM - cell Target ml Target cell cell cell Target Target Target SUBSTITUTE SHEET (RULE 26) cell cell cell Target Target cell cell 1 / 28 my Isolate recognized cell Library of target cells target cells and displaying different Add T cells from sample sequence antigens antigens of interest. CTLs deliver cytotoxic granules to target cells displaying cognate antigen FIG. 1 PCT / US2018 / 036663 20 26 20 53 56 07 J ul 2 02 6 2 0 2 6 2 0 5 3 5 6 0 7 J u l 2 0 2 6 2 0 1 8 / 2 2 7 6 1 o M a n d m y 1 / 2 8 m y L i b r a r y o f t a r g e t c e l l s d i s p l a y i n g d i f f e r e n tA d d T c e l l s f r o m s a m p l e of interest. CTLs deliver c y t o t o x i c g r a n u l e s t o t a r g e t c e l l s d i s p l a y i n g c o g n a t e a n t i g e n P C T / U S 2 0 1 8 / 0 3 6 6 6 3

The application discloses a kind of nanobody specifically targeting human and murine NKG2D protein and its preparation method and application.The nanobody or antigen-binding fragment thereof of the application has three complementarity determining regions CDR1, CDR2 and CDR3;Wherein the amino acid sequences of CDR1, CDR2, CDR3 are as shown in SEQ ID NO.2, SEQ ID NO.3, SEQ ID NO.4 respectively.The nanobody can simultaneously bind hNKG2D and mNKG2D with high affinity, and the bispecific nanobody E5 / 2-B12 based on the nanobody can specifically bind CEACAM5 positive tumor cells and NKG2D overexpression cells, and effectively activate NK cells, which can significantly inhibit tumor growth and prolong survival in various tumor models, and has good application prospect in tumor immunotherapy.

The invention discloses an HER2-CAR lentivirus and application thereof, and belongs to the technical field of lentiviruses. The invention provides the CAR with a brand new structure, the expression level, the stability and the targeting property of the CAR protein in immune cells such as T cells and NK cells can be remarkably improved, the survival time of engineered immune cells in vivo can be prolonged, the lasting anti-tumor capacity of the engineered immune cells can be prolonged, and the tumor cell removing capacity can be improved; the lentiviral vector provided by the invention is high in infection efficiency and wide in host range, provides a reliable platform for large-scale preparation of clinical-grade CAR-T / CAR-NK cell products, and has huge development potential and application value in the field of immunotherapy of HER2 positive solid tumors.

An engineered trophoblast that expresses a cell surface molecule that specifically recognizes NKp46, the cell surface molecule comprising at least an antibody targeting NKp46 and a transmembrane domain. The invention discloses a cell culture medium and a method for amplifying NK cells. Compared with unengineered trophoblasts, the engineered trophoblasts are used for activating NK cells, and the amplification capacity of the NK cells and the killing activity of tumor cells can be enhanced.