32 results about "Human lymphocyte" patented technology

The invention relates to the technical field of medical quality control products, in particular to a quality control substance for lymphocyte subpopulation analysis and a preparation method thereof, and the quality control substance comprises human monocyte simulation particles, human granulocyte simulation particles, human lymphocyte simulation particles, human erythrocyte simulation particles, human platelet simulation particles and a preserving fluid, adding the human monocyte simulation particles, the human granulocyte simulation particles, the human lymphocyte simulation particles, the human erythrocyte simulation particles and the human platelet simulation particles into a preserving fluid, and uniformly mixing according to the concentration of the human body particles, so as to obtain the quality control substance for lymphocyte subpopulation analysis. Compared with the prior art, the quality control substance for lymphocyte subpopulation analysis and the preparation method thereof have the advantages that the preparation method is simple to operate, small in batch difference and good in stability, and can be applied to quality control in the field of detection of quality control substances for flow cytometry lymphocyte subpopulation analysis.

The present invention provides stable pharmaceutical formulations comprising a human antibody that specifically binds to human lymphocyte activation gene-3 (LAG-3). In certain embodiments, the formulations contain, in addition to an anti-LAG-3 antibody, a buffer, an amino acid, a non-ionic surfactant, and a sugar. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability upon stress and storage.

An antigen peptide is provided specifically for treating individuals suffering from ovarian cancer, preferably based on BRCA1 gene c. 5470_5477del8 mutation. It is selected from amino acid sequences of SEQ ID NO. 1 to SEQ ID NO. 6, or derived by substitution, deletion and / or addition of at least one amino acid. The neoantigen polypeptides of the present disclosure can significantly activate T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro, stimulating the release of the cytokine IFN-y, indicating notable immunogenicity. This enhances T lymphocytes' ability to target and kill cancer cells from ovarian cancer patients carrying the BRCA1 gene c. 5470_5477del8 mutation. Additionally, the antigen peptide can activate and expand human T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro for adoptive cell therapy. The antigen peptide of the present disclosure addresses the gap in personalized antigen peptide therapies for ovarian cancer patients with BRCAl-c. 5470_5477del8 somatic mutations.

The present invention provides stable pharmaceutical formulations comprising a human antibody that specifically binds to human lymphocyte activation gene-3 (LAG-3). In certain embodiments, the formulations contain, in addition to an anti-LAG-3 antibody, a buffer, an amino acid, a non-ionic surfactant, and a sugar. The pharmaceutical formulations of the present invention exhibit a substantial degree of antibody stability upon stress and storage.

To provide a novel approach for the expression or regulation of FOXP3 in a primary human lymphocyte.SOLUTION: Aspects of the invention described herein concern the incorporation of a FOXP3 cDNA (e.g., full-length of a human codon-optimized FOXP3 cDNA) into a FOXP3 gene or a non-FOXP3 locus so as to provide constitutive or regulated FOXP3 expression in a primary human CD34+ cells or cells derived from edited CD34+ cells. In some embodiments, guide RNA sequences that are directed to FOXP3, AAVS1, or other candidate loci are used for CRISPR / Cas9-mediated gene regulation, and gene delivery cassettes for homology-directed repair (HDR)-based gene-modification are provided.SELECTED DRAWING: Figure 1

The invention belongs to the technical field of biological extraction, and discloses a separation method for improving the yield of human lymphocytes. The method comprises the following steps: collecting blood cells, diluting the blood cells, obtaining lymphocytes and recovering the lymphocytes. The method is characterized in that a blood cell diluent is prepared and comprises human serum albumin, EDTA-2Na (Ethylene Diamine Tetraacetic Acid-2Na) and a calcium-magnesium ion-free PBS (Phosphate Buffer Solution). The method is applied to lymphocyte separation, the osmotic pressure of cells in the separation process can be improved, the normal form of the cells can be maintained, the viscosity between the cells can be reduced, cell adhesion can be prevented, meanwhile, the part which is adhered to form a membrane layer or a cell cluster is separated twice, the lymphocyte separation yield is remarkably increased, and the method is simple to operate and easy to implement. The realization is easy. The method is especially suitable for blood samples of people with immune system diseases, blood samples and blood viscous samples of old and sick people, non-fresh blood samples and the like.

The present disclosure relates to cell therapy methods for treating solid carcinoma tumors comprising administration of immune cells expressing a chimeric antigen receptor (CAR) comprising a mutant I domain of the αL subunit of human lymphocyte function-associated antigen-1 (LFA-1), which are cytotoxic against solid carcinoma tumors overexpressing ICAM-1 and alleviate on-target, off-tumor toxicities.

The invention relates to a quality control substance for flow cytometry HLA-B27 analysis as well as a preparation method and application of the quality control substance. The quality control substance comprises a negative quality control substance and a positive quality control substance; the negative quality control substance comprises human lymphocyte negative quality control substance simulation particles and human peripheral blood cells or simulation particles; an HLA-B27 antigen is not expressed on the surface of the human lymphocyte negative quality control substance mimic particle; the positive quality control substance comprises human lymphocyte positive quality control substance simulation particles and human peripheral blood cells or simulation particles; an HLA-B27 antigen is expressed on the surface of the human lymphocyte positive quality control substance simulation particle; cD3 antigens and CD45 antigens are expressed on the surfaces of the human lymphocyte positive quality control substance simulation particles and the human lymphocyte negative quality control substance simulation particles. The technical problem to be solved is how to provide a quality control substance which is good in stability and can be applied to flow cytometry HLA-B27 analysis.

The present disclosure relates to cell therapy methods for treating solid carcinoma tumors comprising administration of immune cells expressing a chimeric antigen receptor (CAR) comprising a mutant I domain of the αL subunit of human lymphocyte function-associated antigen-1 (LFA-1), which are cytotoxic against solid carcinoma tumors overexpressing ICAM-1 and alleviate on-target, off-tumor toxicities.

The invention belongs to the technical field of cell culture, and particularly relates to a method for preparing Jurkat cells on a large scale by utilizing a bioreactor. The preparation method comprises the following steps: (1) cell resuscitation: resuscitating cells from liquid nitrogen; (2) carrying out cell multiplication culture: carrying out step-by-step amplification multiplication culture in T bottles and cell culture bags with different specifications; (3) large-scale culture of cells: performing large-scale culture by using a bioreactor; and (4) harvesting the cells: collecting the cell suspension, and centrifugally harvesting the cells. The preparation method overcomes the problem that a large number of thymus cells or human lymphocytes need to be used as immunogens when the anti-human T lymphocyte immune globulin is prepared, can simply and quickly prepare a large number of Jurkat cells, is used for preparing the anti-human T lymphocyte immune globulin, improves the quality, reduces the biological safety risk, and has a wide application prospect. The method is beneficial to industrial production and has a relatively good economic effect.

The present invention relates to a modified human lymphocyte containing and expressing a recombinant nucleic acid or a set of recombinant nucleic acids encoding at least one positive regulator of autophagy. The modified human lymphocyte according to the invention may further contain and express a recombinant nucleic acid or a set of recombinant nucleic acids encoding a T-cell receptor or a chimeric antigen receptor. The invention also relates to methods of producing such modified human lymphocytes, pharmaceutical compositions comprising the same, as well as their uses in medicine and for methods for the treatment of cancer including the immunotherapeutic treatment of cancer.

The present invention relates to modified human lymphocytes comprising and expressing a recombinant nucleic acid or set of recombinant nucleic acids encoding at least one positive autophagy regulator. The modified human lymphocytes according to the present invention may also comprise and express recombinant nucleic acids or groups of recombinant nucleic acids encoding T cell receptors or chimeric antigen receptors. The invention also relates to methods of producing such modified human lymphocytes, pharmaceutical compositions comprising them, and their use in medicine and for methods of treatment of cancer, including immunotherapeutic treatment of cancer.

The invention relates to a CpGODN molecule and an application thereof. According to the CpG adjuvant, by optimizing a core CpG motif (such as 5 '-GACGTT-3') and a flanking sequence thereof, the activation efficiency of a Toll-like receptor 9 (TLR9) is remarkably improved. In order to further enhance the stability and the targeting property of the CpG adjuvant, the CpG oligonucleotide is subjected to phosphorothioate modification, and the CpG adjuvant shows excellent immune activation ability in both in-vitro and in-vivo experiments, can significantly enhance the immunogenicity of vaccines, overcomes the species effect, has a good stimulation effect on both mouse and human lymphocytes, and can be used for preparing the immunopotentiator. The compound has a remarkable synergistic effect with an aluminum adjuvant, realizes relatively balanced cell humoral immune response, and has a wide application prospect in the field of vaccine development.

The present invention relates to chimeric antigen receptors (CARs) specific to ICAM-1 comprising I domain of the αL subunit of human lymphocyte function-associated antigen 1 (LFA-1). The invention particularly relates to CARs comprising human I domains having different affinities (1 mM to 1 nM Kd) to ICAM-1. CAR T cells comprising human I domain having a low affinity (1 to 200 μM Kd) to ICAM-1 can avoid targeting healthy tissues with basal ICAM-1 expression while simultaneously exhibiting increased potency and long-term efficacy against tumor tissues with high ICAM-1 expression. The present invention also relates to an adoptive cell therapy method for treating cancer by administering the CAR-T cells comprising human I domain to a subject suffering from cancer, whereby the CAR T cells bind to the cancer cells overexpressing ICAM-1 and kill the cancer cells.

The present disclosure relates to cell therapy methods for treating solid carcinoma tumors comprising administration of immune cells expressing a chimeric antigen receptor (CAR) comprising a mutant I domain of the αL subunit of human lymphocyte function-associated antigen-1 (LFA-1), which are cytotoxic against solid carcinoma tumors overexpressing ICAM-1 and alleviate on-target, off-tumor toxicities.

The present application relates to the technical field of medical quality control products, in particular to a quality control substance for lymphocyte subset analysis and a preparation method thereof, comprising human monocyte simulation particles, human granulocyte simulation particles, human lymphocyte simulation particles, human red blood cell simulation particles, human platelet simulation particles and a preservative, wherein the human monocyte simulation particles, the human granulocyte simulation particles, the human lymphocyte simulation particles, the human red blood cell simulation particles and the human platelet simulation particles are added into the preservative, and mixed according to the concentration of human particles to obtain the quality control substance for lymphocyte subset analysis. Compared with the prior art, the quality control substance for lymphocyte subset analysis and the preparation method thereof have the advantages of simple operation, small batch difference and good stability, and can be applied to the field of quality control of flow cytometry methodological lymphocyte subset analysis.

The present invention relates to a specific type of non-porous and non-magnetic composite material consisting of a solid surface having a specific diameter and an antigen recognition element for use in a method for activating and amplifying T lymphocytes.

To provide compositions and materials that facilitate constitutive or regulated FOXP3 expression in a primary human lymphocyte by targeting a FOXP3 cDNA into a FOXP3 locus or a non-FOXP3 locus.SOLUTION: The compositions and materials provide specificity for CRISPR / Cas-mediated gene regulation of murine, non-human primates or human FOXP3. Guide RNA sequences are used to target the FOXP3, AAVS1, and other candidate loci for CRISPR / Cas-mediated gene regulation, and gene delivery cassettes for homology-directed repair-based gene-modification are provided.SELECTED DRAWING: None

The present disclosure relates to cell therapy methods for treating solid carcinoma tumors comprising administration of immune cells expressing a chimeric antigen receptor (CAR) comprising a mutant I domain of the αL subunit of human lymphocyte function-associated antigen-1 (LFA-1), which are cytotoxic against solid carcinoma tumors overexpressing ICAM-1 and alleviate on-target, off-tumor toxicities.

The present disclosure relates to in vitro mammalian, e.g., human, lymphoid cell cultures and systems, and the utility of these culture and systems for determining the immunogenicity of candidate therapeutic molecules. The present disclosure also relates to in vitro methods of antibody production utilizing the disclosed lymphoid cell cultures.

Provided are a human B lymphocyte stimulator receptor (TACI) antibody having high specificity and high affinity for TACI, and a method for detecting TACI or a TACI-Fc fusion protein by using the TACI antibody. By means of the method, the content of a free TACI or TACI-Fc fusion protein drug in a patient can be detected, and the level of drug absorption in the patient is effectively known according to the content of the drug in the patient, thereby achieving the effects of evaluating the illness state, monitoring the efficacy, and determining the prognosis of a patient with an autoimmune disease.

An antigen peptide is provided specifically for treating individuals suffering from ovarian cancer, preferably based on BRCA1 gene c. 5470_5477del8 mutation. It is selected from amino acid sequences of SEQ ID NO. 1 to SEQ ID NO. 6, or derived by substitution, deletion and / or addition of at least one amino acid. The neoantigen polypeptides of the present disclosure can significantly activate T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro, stimulating the release of the cytokine IFN-y, indicating notable immunogenicity. This enhances T lymphocytes' ability to target and kill cancer cells from ovarian cancer patients carrying the BRCA1 gene c. 5470_5477del8 mutation. Additionally, the antigen peptide can activate and expand human T lymphocytes specific to the BRCA1 gene c. 5470_5477del8 mutation in vitro for adoptive cell therapy. The antigen peptide of the present disclosure addresses the gap in personalized antigen peptide therapies for ovarian cancer patients with BRCAl-c. 5470_5477del8 somatic mutations.

The invention discloses a universal chimeric antigen receptor T cell, the universal chimeric antigen receptor comprises an extracellular region, a transmembrane region and an intracellular region, the intracellular region comprises an intracellular signal transduction region, and the intracellular region further comprises a lectin-like transcript 1 (LLT1) molecule directly or indirectly connected to the tail end of the intracellular signal transduction region. When being applied to clinical treatment, the universal CAR-T cell provided by the invention can be put into standardized mass production, and T lymphocytes of a patient do not need to be collected during treatment, so that the universal CAR-T cell is not limited by the condition of the patient and a treatment method. And the patient selecting the universal CAR-T can be treated in time without delaying the illness state. Healthy human lymphocytes have higher activity and functions, and the universal CAR-T prepared from the healthy human lymphocytes can have higher CAR positive rate and cell proliferation level, so that the universal CAR-T can play a more remarkable treatment effect on the condition of a patient.

The present invention provides stable pharmaceutical formulations comprising a human antibody that specifically binds to human Lymphocyte-Activation Gene-3 (LAG-3). In certain embodiments, the formulations comprise, in addition to the anti-LAG-3 antibody, a buffer, an amino acid, a non-ionic surfactant, and a sugar. The pharmaceutical formulations of the present invention exhibit a considerable degree of antibody stability upon stress and storage.

The invention discloses an immune cell killing activity detection method based on fluorescently labeled tumor target cells, and relates to the technical field of detection.The immune cell killing activity detection method comprises the steps that peripheral blood or umbilical cord blood of a healthy volunteer is collected, mononuclear cells are obtained through separation with a human lymphocyte separation medium and induced into immune effector cells, and multiplication culture is conducted; taking the fluorescently-labeled tumor cells as target cells, and co-incubating the immune effector cells and the target cells for a period of time; collecting a cell product after co-incubation is finished, and detecting the number of fluorescently-labeled positive cells in the co-incubation product by using a flow cytometer or a fluorescent cell counter; and calculating the killing rate of the immune effector cells to the target cells based on the detected number of the positive cells. The scheme is simple and convenient to operate, rapid, accurate, low in cost and free of cell damage.

The invention relates to a probe composition for detecting intracellular EBV, the probe composition comprises a basic probe and a fluorescent probe, the basic probe is hybridized and paired with intracellular EBV virus mRNA, and the fluorescent probe is hybridized and paired with the basic probe; the mRNA corresponds to an EBV virus lysis period and / or incubation period gene region. The probe composition disclosed by the invention can be widely applied to EB diagnostic reagents, curative effect evaluation and / or safe drug withdrawal of anti-EB virus treatment, and treatment endpoint monitoring of the EB virus diagnostic reagents.

The invention relates to a lymphocyte simulation composition, a preparation method, a quality control substance and a quality control method. The lymphocyte simulation composition comprises lymphocyte simulation particles stored in a preservation solution, the volume ratio of the lymphocyte simulation particles in the composition is 50% or above, the lymphocyte simulation particles are obtained by treating lymphocytes separated from blood of mammals, and the lymphocyte simulation particles are used for simulating the lymphocytes. When the lymphocyte simulation particle is tested by a hematology analyzer, the lymphocyte simulation particle has the same or similar light scattering characteristics as human lymphocytes, and the light scattering characteristics at least reflect the complexity of cell contents. By independently preparing the lymphocyte simulation particles, the particles have good consistency and stability, and the obtained composition has small batch-to-batch difference when serving as a quality control substance, so that the quality control of a hematology analyzer is facilitated, and the reliability of clinical examination of the hematology analyzer is improved.

The application discloses a kind of containing isoindole ketone spleen tyrosine kinase inhibitor and its preparation method and application, belong to the technical field of medicinal chemistry.The application uses active group splicing method, retains the trimethoxy phenyl and pyrimidine of Fostamatinib structure as parent nucleus, replaces pyridoxylidene oxazinone with isoindole ketone, designs and synthesized 16 target compounds (general formula is shown below), and test the antitumor, antibacterial and anti-inflammatory activity of the compound, wherein, compound 6a is superior to positive control drug on the inhibition of human B lymphocyte (Raji), 6l on human breast cancer cell (MCF-7) and 6j human hepatoma cell (HepG2);Compound 6l has the best antibacterial activity, 6i and 6j are better than positive control drug Fostamatinib in anti-inflammatory activity, therefore, the isoindole ketone-containing spleen tyrosine kinase inhibitor of the application has good development prospect.

Provided are methods of generating cells that produce monoclonal antibodies that specifically bind domain 2 of a human lymphocyte activation gene-3 (LAG-3) polypeptide. The methods comprise immunizing a non-human animal with an immunogen comprising domain 2 of a human LAG-3 polypeptide and isolating monoclonal antibody-producing cells from the non-human animal, wherein the monoclonal antibody-producing cells produce monoclonal antibodies that specifically bind the immunogen. Such methods further comprise screening the monoclonal antibody-producing cells for cells that produce monoclonal antibodies that specifically bind domain 2 of human LAG-3. Also provided are in vitro methods of identifying a polypeptide that specifically binds domain 2 of a human LAG-3 polypeptide, as well as in silico methods of identifying an agent as a candidate human LAG-3 dimerization disrupting agent. Antibodies, polypeptides and agents identified according to the methods of the present disclosure are also provided.

The present invention provides compounds and methods of targeting human lymphocyte chemokines, including therapeutic antibodies, pharmaceutical compositions, and methods of use thereof, for use in the fields of immune-mediated diseases including ulcerative colitis, vitiligo, multiple sclerosis, alopecia areata, psoriasis, type 1 diabetes, and asthma.