1360 results about "Lymphocyte" patented technology

To provide antibodies that bind to lymphocyte activation gene 3 (LAG3) protein, which is a T cell co-inhibitor, and methods of use.SOLUTION: In various embodiments of the invention, the antibodies are fully human antibodies that specifically bind to LAG3. In some embodiments, the antibodies of the invention are useful for inhibiting or neutralizing LAG3 activity, thus providing means of treating a disease or disorder such as cancer or viral infection. The antibodies of the present invention are useful, inter alia, for targeting immune cells expressing LAG3 and for modulating LAG3 activity.SELECTED DRAWING: None

The present invention relates to an immunomicrobubble complex and its uses. The immunomicrobubble complex (IMC) according to the present invention comprises microbubbles conjugated with an antibody, wherein the microbubbles have excellent stability and excellent antibody binding strength, and it has been confirmed that when the immunomicrobubble complex is treated with high-intensity focused ultrasound (HIFU), the anti-tumor effect is significantly enhanced and an immune-enhancing effect is exhibited. Therefore, the immunomicrobubble complex according to the present invention is expected to improve the delivery efficiency of the conjugated antibody and can be used for the diagnosis and treatment of cancer, and exhibits various functions in the field of immunotherapy, including a contrast effect, improvement of half-life, improvement of drug delivery, lymphocyte concentrating effect, cancer immunotherapy, and ultrasound-induced immunotherapy.

This disclosure provides a method for treating a subject afflicted with a lung cancer, which method comprises administering to the subject therapeutically effective amounts of: (a) an antibody or an antigen-binding portion thereof that specifically binds to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity; and (b) an antibody or an antigen-binding portion thereof that specifically binds to a Cytotoxic T-Lymphocyte Antigen-4 (CTLA-4) and inhibits CTLA-4 activity.

Provided herein are lentiviral vectors comprising a mutated, heterologous envelope protein, a targeting protein, and at least one transgene for delivery to and expression by a cell characterized by the targeting protein. Also provided are methods and materials for producing the lentiviral vectors described herein, methods for transducing target cells, and cells transduced by lentiviral vectors according to the present disclosure.

The disclosure provides a method of treating a human subject afflicted with lung cancer (e.g., non-small cell lung cancer (NSCLC)) with a programmed death-1 (PD-1) pathway inhibitor (e.g., an anti-PD-1 antibody) and a concurrent chemoradiotherapy (CCRT, e.g., a platinum doublet chemotherapy (PDCT) and a radiation therapy) followed by a combination of a PD-1 pathway inhibitor (e.g., an anti-PD-1 antibody) and a lymphocyte activation gene-3 (LAG-3) antagonist (e.g., an anti-LAG-3 antibody). In some aspects, the method comprises a recovery period that begins upon completion of the treatment with the PD-1 pathway inhibitor and the CCRT and ends at the start of the treatment with the combination of the PD-1 pathway inhibitor and the LAG-3 antagonist.

The present invention relates to T lymphocytes targeting CLD18A2 and a preparation method and application thereof. The inventors have successfully found a target gene CLD18A2 suitable for developing CAR T cells from a number of tumor-related genes for the first time, and successfully prepared CAR T cells targeting CLD18A2, thereby providing a new treatment method for pancreatic cancer, gastric cancer and other tumors.

The invention belongs to the technical field of inspection and extraction, and particularly relates to an automatic T lymphocyte suction device which comprises an automatic suction device body, the automatic suction device body comprises a bearing table, a rotating disc with a circumferential rotating function is arranged on the bearing table, and a plurality of centrifugal assemblies are evenly distributed on the rotating disc. A centrifugal tube feeding assembly facilitating feeding of centrifugal tubes is arranged in front of one side of the bearing table, a tube carrying and conveying assembly is arranged on the portion, located on one side of the centrifugal tube feeding assembly, of the bearing table, a tube feeding mechanism is arranged at the end of the conveying belt mechanism, and a reaction reagent adding assembly is arranged on one side of the tube carrying and conveying assembly. A sample feeding assembly is arranged on one side of the upper portion of the workbench, and a first suction assembly is arranged above the multi-direction adjusting assembly. According to the invention, multiple samples can be processed in batches, the working efficiency and the cell extraction purity are improved, the influence of manual operation on the result is reduced, the accuracy of the detection effect is ensured, and the use requirements are met.

Described herein are novel and improved antibodies that bind to thymic stromal lymphopoietin (TSLP) and methods of use thereof. In certain aspects, described herein are methods of inhibiting TSLP biological activity. In certain aspects, the antibodies and methods described herein are used for treatment of an inflammatory disease or disorder associated with elevated levels of TSLP. In certain aspects, described herein are methods of treating asthma by administering anti-TSLP antibodies.

Provided are adoptive cell therapy methods involving the administration of doses of cells for treating B cell malignancies. The cells generally express recombinant receptors such as chimeric antigen receptors (CARs). In some embodiments, the methods are for treating subjects with chronic lymphocytic leukemia (CLL). In some embodiments, the methods are for treating subjects with non-Hodgkin lymphoma (NHL). In some embodiments, the methods involve prior administration of a lymphodepleting therapy, such as prior administration of fludaribine and / or another lymphodepleting chemotherapeutic agent, for example cyclophosphamide. In some embodiments, features of the methods include an increase in complete remission, overall survival and / or progression free survival of subjects treated in accord with the provided methods.

An anti-PD1 (programmed cell death 1) monoclonal antibody or an antigen-binding fragment thereof, a pharmaceutical composition thereof and use thereof. The heavy chain variable region of the monoclonal antibody comprises CDRs (complementary determining region) of amino acid sequences as shown in SEQ ID NO:9-11; and / or the light chain variable region of the monoclonal antibody comprises CDRs of amino acid sequences as shown in SEQ ID NO: 12-14. The monoclonal antibody can bind to PD1 specifically, relieve immunosuppression of PD1 on an organism specifically and activate T lymphocytes.

The present invention provides improved and / or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

The invention discloses a pharmaceutical composition for promoting aTreg cell differentiation and application thereof, and relates to the field of biological medicine, and the pharmaceutical composition comprises zinc salt, a basic cell culture medium, fetal calf serum, antibiotic, L-glutamine and a pH buffer agent. According to the application, the basic cell culture medium is used for providing basic nutrition required by cell growth for lymphocytes, the fetal calf serum is used for providing growth factors, hormones, adhesion proteins and nutrient substances required by cell growth for the lymphocytes, and the antibiotics are used for preventing bacterial infection; l-glutamine provides key amino acid for cell energy metabolism and participates in synthesis of protein and nucleic acid, zinc salt provides zinc ions, and under the comprehensive action, the proportion of Treg cells and aTreg cells differentiated from lymphocytes in peripheral blood mononuclear cells is increased.

The invention discloses a reagent for rapidly distinguishing bacterial and virus infection and application, belongs to the field of molecular biology, relates to medical and biotechnology, and aims to solve the problem that a traditional method cannot clearly distinguish bacterial infection from virus infection. The reagent comprises five antibodies marked with different fluorescence. The five antibodies are all mouse anti-human or rabbit anti-human antibodies, and targets corresponding to the five antibodies are respectively CD45, CD14, CD64, CD169 and HLA-DR (human leukocyte antigen-DR). The tail end of the antibody is connected with different fluorescein through chemical reaction; fluorescence labeling is performed on neutrophils, mononuclear cells and lymphocytes in peripheral blood through an antibody combination of CD molecules, and corresponding infection indexes are calculated through a flow cytometry method, so that the infection type (bacterial / virus infection) of a patient is quickly distinguished and judged.

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.

The invention belongs to the field of traditional Chinese medicines, and particularly relates to a traditional Chinese medicine composition for treating triple negative breast cancer and application thereof. The traditional Chinese medicine composition is prepared from the following main active ingredients in parts by mass: 20 to 40 parts of radix astragali seu hedysari, 10 to 20 parts of rhizoma curcumae, 10 to 20 parts of herba hedyotidis diffusae, 5 to 15 parts of fructus aurantii immaturus, 5 to 15 parts of radix bupleuri, 5 to 15 parts of radix paeoniae alba and 5 to 15 parts of liquorice root. Animal experiments show that the traditional Chinese medicine composition can significantly inhibit tumor growth and pulmonary metastasis of triple-negative breast cancer tumor-bearing mice, increase the proportion of CD8 + T lymphocytes in blood, reduce the proportion of MDSCs, significantly down-regulate the expression of pro-inflammatory cytokines such as IL-6, IL-1alpha, CXCL1 and GM-CSF in serum, and cooperate with PD-L1 immunotherapy to achieve a synergistic effect. And the whole blood and liver and kidney function indexes are in a normal range. Therefore, the traditional Chinese medicine composition disclosed by the invention can be used for effectively inhibiting the tumor growth and pulmonary metastasis of the triple negative breast cancer, remodeling the immune state of an organism and reducing the release of proinflammatory factors, and is safe, reliable, free of obvious liver and kidney toxicity and blood toxicity and small in side effect.

Disclosed are an antibody capable of binding to thymic stromal lymphopoietin and the use thereof. Disclosed are an anti-TSLP antibody, comprising a murine antibody, chimeric antibody and humanized antibody of the light chain and heavy chain variable regions of the anti-TSLP antibody and antigen-binding fragments thereof, or a pharmaceutically acceptable salt or solvent compound thereof, and the use thereof as a medicament for treating asthma, especially the use thereof in the preparation of a drug for treating TSLP-positive diseases or conditions.

The invention provides an application of a T lymphatic activation related cytokine as a biomarker in prediction of children immune globulin non-reactive Kawasaki disease. The team finds that in patients of an IVIG sensitive group and an IVIG non-response group, differences of expression levels of IL-6 and IL-17 before and after treatment have statistical significance; meanwhile, ROC curve analysis shows that IL-6 and IL-17 serve as early warning signals, and the prediction efficiency of the IVIG-unreacted Kawasaki disease is remarkably superior to that of existing prediction factors. Particularly, the levels of IL-6 and IL-17 are re-evaluated after initial treatment, so that the early prediction accuracy of the IVIG unresponsive Kawasaki disease can be further improved. By introducing IL-6 and IL-17 as novel biomarkers, early accurate prediction of the IVIG unresponsive Kawasaki disease is realized. Compared with the prior art, the method can provide a quicker and more accurate risk assessment basis for clinicians, so that early recognition of high-risk patients, optimization of subsequent treatment schemes and reduction of serious complications are facilitated, and a new thought and direction are provided for clinical diagnosis and treatment.

The present invention provides improved and / or shortened processes and methods for preparing TILs in order to prepare therapeutic populations of TILs with increased therapeutic efficacy for the treatment of non-small cell lung carcinoma (NSCLC), wherein the NSCLC is refractory to treatment with an anti-PD-1 antibody and / or anti-PD-L1 antibody and / or VEGF inhibitor, or wherein the NSCLC has a predetermined tumor proportion score (TPS).

The invention discloses a method for culturing CIK (Cytokine-Induced Killer) cells and application thereof. The method comprises the following steps: recovering cord blood, mixing and centrifuging the recovered cord blood and a buffer solution, re-suspending and precipitating, centrifuging again to obtain cord blood mononuclear cells, inoculating the cord blood mononuclear cells into an activation culture medium, and culturing to obtain the CIK cells, the buffer solution contains L-proline, human recombinant DNA enzyme and angelica polysaccharide. According to the method, the mononuclear cells can be separated from the umbilical cord blood preserved by liquid nitrogen, the utilization rate of the umbilical cord blood which can only be discarded due to insufficient cells is increased, the traditional lymphocyte separation process is optimized, the recovery rate of the mononuclear cells is increased, and the cost is reduced. The method provided by the invention can be used for culturing dozens to ten billions of CIK cells from a small amount of cryopreserved cord blood, and has huge advantages in the field of CIK cell culture and application.

The present invention belongs to the technical field of monoclonal antibody preparation, and specifically relates to a method for preparing a universal whole-pig monoclonal antibody. The present invention is based on single B cell antibody preparation technology, and antigen-specific single B lymphocytes are separated from the peripheral blood of immune pigs or clinically recovered pigs by flow cytometry sorting technology; according to the pig immunoglobulin IgG antibody gene sequence in the database, primers are designed to specifically amplify the complete coding genes of antibody heavy and light chains in pig single B cells and add His tags, and pCDNA3.1-Leader is used as a eukaryotic expression vector to construct a recombinant vector of complete coding genes for antibody light and heavy chains, and natural whole-pig monoclonal antibodies are expressed by mammalian cells. The present invention establishes a universal whole-pig monoclonal antibody preparation method for the first time, which can be used for the preparation and screening of pig monoclonal antibody libraries of different pathogens. Compared with other antibody preparation methods, it has the advantages of high throughput, whole pig source, good diversity, complete antibodies and natural pairing, etc., which provides technical support for the rapid preparation and screening of pig monoclonal antibodies and has broad application prospects.

The present invention provides improved and / or shortened methods for expanding TILs and producing therapeutic populations of TILs, including novel methods for expanding TIL populations in a closed system that lead to improved efficacy, improved phenotype, and increased metabolic health of the TILs in a shorter time period, while allowing for reduced microbial contamination as well as decreased costs. Such TILs find use in therapeutic treatment regimens.

The invention belongs to the technical field of biological medicines, and particularly discloses a nano-engineering T cell membrane coated nano-particle as well as a preparation method and application of the nano-engineering T cell membrane coated nano-particle. Nanoparticles of a specific structure are constructed based on a phospholipid bilayer bionic nanometer platform through a membrane fusion technology, immune clearance caused by phagocytosis of the nanoparticles by macrophages can be avoided through disguise of a T cell membrane, and the blood circulation time is prolonged; the functions of T cells are recovered through specific blocking of immune checkpoint molecules loaded on the immune checkpoint molecules on corresponding immune checkpoint ligands on tumor cells; under ultrasonic radiation, the nano-particles are gradually decomposed and release the sound-sensitive agent to generate a large amount of active oxygen, so that immunogenic death of tumor cells is promoted, more cytotoxic T lymphocytes are recruited to infiltrate into tumor parts, and the recovery of T cell mediated immune response function is facilitated. The synergistic effect of the sound-sensitive agent and the immune checkpoint protein can effectively inhibit tumor growth, induce a long-term immune memory effect and prevent tumor metastasis and recurrence.

The present application relates to conjugates comprising an amatoxin, a target-binding moiety wherein the target is CD37, i.e., a CD37-binding moiety, and optionally a linker linking said amatoxin and said CD37-binding moiety. The invention further relates to the synthesis of said conjugates. In addition, the invention relates to a pharmaceutical composition comprising such conjugate for use in the treatment of immune cell, particularly B-cell and / or lymphoma associated diseases and / or malignancies (FIG. 1).

The invention belongs to the technical field of biological medicines, and particularly relates to an antigen peptide library for inducing tumor specific immune response, the antigen peptide library comprises eight antigen peptides, and the amino acid sequences of the eight antigen peptides are respectively shown as SEQ ID NO.1-SEQ ID NO.8. The invention further discloses a preparation method of the antigen peptide library. The antigen peptide has high immunogenicity and can effectively stimulate and induce generation of specific cytotoxic T lymphocytes when being loaded on antigen presenting cells, in-vitro killing experiments show that CTL cells induced and activated by loading new antigen DC have a high tumor killing effect, and the cell killing activity of the CTL cells is 90% or above. When model mice are treated by adoptive T cell back-transfusion of CTL cells induced by the new antigen peptide library, the tumor volume can be effectively reduced, the survival rate of the tumor can be remarkably increased, and good treatment potential is achieved.

The invention relates to stable formulations comprising antibodies or antigen binding fragments thereof that bind to cytotoxic T lymphocyte associated antigen 4 (CTLA4), optionally further containing an anti-human programmed death receptor 1 (PD-1) antibody or antigen binding fragment thereof. Also provided are methods of treating various cancers and chronic infections with the formulations of the invention.

The invention provides an application of a spleen T lymphocyte exosome in construction of a depression animal model, a stress rat spleen T lymphocyte exosome is injected into a mouse body to construct the depression animal model, and the depression animal model can be used for depression drug screening, drug efficacy evaluation or diagnosis, and can be used for treating depression. And the method can also be used for researching and revealing pathogenesis of depression. The invention also proves that the IL4 / IL4R alpha signal channel and the BDNF signal channel play an important role in depression through experiments. The invention has important significance for clinical research of depression.

The invention relates to the technical field of medical treatment, and particularly discloses a compound prognosis model for cancer prognosis evaluation, a prognosis evaluation method and a calculator. The compound prognosis model is constructed based on inflammation burden related prognosis indexes ALNCR and TNM by stage combination; the creation method comprises the following steps: step 1, collecting albumin concentration, lymphocyte count, neutrophil count and C-reactive protein concentration data of a cancer patient; 2, calculating an ALNCR index according to a formula; 3, according to a clinical classic TNM staging system, the patients are divided into a TNM staging stage I, a TNM staging stage II, a TNM staging stage III or a TNM staging stage IV; 4, the ALNCR index obtained in the step 2 and the TNM staging result obtained in the step 3 are associated and integrated, and the individualized prognosis score of the ALNCR.TNM composite prognosis model is obtained through calculation. The method is suitable for clinical rapid application; high-risk patients can be accurately distinguished, a quantitative basis is provided for individualized treatment and follow-up visit strategy formulation, and excessive medical treatment or insufficient treatment is reduced.

The present invention provides isolated monoclonal antibodies that specifically bind LAG-3, and have optimized functional properties compared to previously described anti-LAG-3 antibodies, such as antibody 25F7 (US 2011 / 0150892 A1). These properties include reduced deamidation sites, while still retaining high affinity binding to human LAG-3, and physical (i.e., thermal and chemical) stability. Nucleic acid molecules encoding the antibodies of the invention, expression vectors, host cells and methods for expressing the antibodies of the invention are also provided, as well as immunoconjugates, bispecific molecules and pharmaceutical compositions comprising the antibodies. The present invention also provides methods for detecting LAG-3, as well as methods for treating stimulating immune responses using an anti-LAG-3 antibody of the invention. Combination therapy, in which the antibodies are co-administered with at least one additional immunostimulatory antibody, is also provided.

The invention relates to the technical field of small molecule medicines, in particular to a medicine for improving chronic atrophic gastritis and application of the medicine. The invention aims to provide a compound, a pharmaceutical composition containing the compound and application of the compound, the 9, 13-substituted berberine derivative has a good improvement effect on CAG, and further research and observation of the compound on treatment of CAG gastric mucosa gland epithelial cell atrophy, gastric mucosa thinning, gastric mucosa epithelial cell atrophy, gastric mucosa hyperplasia, gastric mucosa epithelial cell atrophy and gastric mucosa hyperplasia. The 9, 13-substituted berberine derivative disclosed by the invention can be used for preventing and / or treating CAG (chorionic gonadotrophin) by virtue of the inhibition effects on infiltration adhesion of a large number of neutrophils and lymphocytes, inflammatory factors and the like.

Described herein are antibodies, or antigen binding fragments thereof, that bind thymic stromal lymphopoietin (TSLP) and OX40L in combination and methods of use thereof. In certain aspects, described herein are methods of inhibiting OX40L and TSLP biological activity. In certain aspects, described herein are pharmaceutical compositions comprising the anti-TSLP and anti-OX40L antibodies, or antigen binding fragments thereof. In certain aspects, the antibodies and methods described herein are used for treatment of an inflammatory disease or disorder associated with elevated levels of TSLP and / or OX40L.