231 results about "Lymph Cell" patented technology

Methods of expanding tumor infiltrating lymphocytes (TILs) using a tumor necrosis factor receptor superfamily (TNFRSF) agonist, such as a 4-1BB agonist, a CD27 agonist, a glucocorticoid-induced TNF receptor-related agonist, an OX40 agonist, a HVEM agonist, or a CD95 agonist, and uses of such expanded TILs in the treatment of diseases such as cancer are disclosed herein. In addition, in some embodiments, therapeutic combinations of TILs and TNFRSF agonists useful in the treatment of diseases such as cancer, including compositions, uses, and dosing regimens thereof, are disclosed herein.

In some embodiments, methods of expanding tumor infiltrating lymphocytes using AKT pathway inhibitors and methods of using the expanded tumor infiltrating lymphocytes in the treatment of human diseases, including cancers, are disclosed.

The invention relates to the field of biological medicines, in particular to a chimeric cytokine activated receptor for activating lymphocytes by using soluble immunosuppressive molecules and application of the chimeric cytokine activated receptor in tumor treatment. The chimeric cytokine activation receptor and a chimeric antigen receptor for recognizing tumor antigens are connected in parallel to form a co-expressed polycistron structure. Wherein the chimeric cytokine activation receptor comprises an scFv structural domain, a transmembrane structural domain and a cytokine chimeric activation structural domain which specifically recognize and bind soluble immunosuppressive molecules. The CAR-NK cell can specifically recognize soluble inhibitory factors in the tumor microenvironment and improve the in-vivo and in-vitro anti-tumor efficacy of the CAR-NK cell, and can be used for treating solid malignant tumors.

The present disclosure provides a PD1 targeted novel IL-2 VitoKine composition, featuring a high-affinity PD1 antibody domain and a bio-activable IL- 2 domain with optimally reduced potency. The PD1 Ab-IL2 VitoKine platform mitigates IL-2 therapy-related toxicities and synergizes the anti-tumor effects of PD1 and IL- 2 by: 1) efficiently targeting an inert IL-2 directly to tumor-infiltrating lymphocytes (TILs); 2) ensuring highly tumorspecific activation of the IL- 2 domain by TME- enriched proteases that co-localized with TILs; 3) allowing PD1 Ab and activated IL- 2 to act on intratumoral CD8+T cells in cis. The VitoKine demonstrates greatly enhanced concealment efficiency and has a lower intrinsic basal activity than what would typically be expected from the VitoKine platform incorporating a non-attenuated IL-2. This improvement permits a substantially higher dose tolerance, enabling safe administration at efficacious dose levels of the PD1 antibody, reversing T- cell anergy or exhaustion and further synergizing with IL-2 mediated anticancer immune response.

The present invention relates to assays, methods, and kits to assess traumatic brain injury (TBI) in a subject. The present invention also relates to ultrasensitive assays for GFAP, tau, CKBB, IL-1β, IL-2, IL-6, IL-10, IL-22, IP-10, TNFα, TSLP, NFL, and / or NFH.

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. The methods may comprise gene-editing at least a portion of the TILs to enhance their therapeutic efficacy. Such TILs find use in therapeutic treatment regimens.

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 gene-edited tumor infiltrating lymphocyte and a T cell receptor engineered T cell and application thereof in immunotherapy. According to the invention, NR4A1 and / or NR4A2 and / or NR4A3 genes are / is knocked out from tumor infiltrating lymphocytes or T cell receptor engineered T cells, so that the multiplication capacity and the anti-tumor capacity of the tumor infiltrating lymphocytes or T cell receptor engineered T cells are improved.

The invention discloses a trophoblast-free one-step culture method and application of tumor infiltrating lymphocytes, and particularly discloses a one-step amplification method of tumor infiltrating lymphocytes, which comprises the following steps: treating a tumor sample obtained from a subject into tumor segments; the tumor segments are cultured in a culture medium containing a CD3 agonist, a 4-1BB agonist and IL-2, so that an amplified tumor infiltration lymphocyte population is obtained, and the culture medium does not contain trophoblastic cells. Compared with the prior art, the method has the advantages that the required period for amplifying the tumor infiltrating lymphocytes is shorter, the cost is lower, the cell effect function is stronger, and the clinical application range of the tumor infiltrating lymphocyte therapy is widened.

The invention provides pathological tissue section dyeing equipment and method. The method comprises the following steps: dividing a to-be-dyed lymphatic tissue section into a plurality of dyeing partitions according to the structural characteristics of lymphocyte tissues in the to-be-dyed lymphatic tissue section; dyeing agents with different concentrations are applied to different dyeing partitions according to the reference light transmittance of the lymphocyte tissue to obtain color gradient vectors of the lymphocyte tissue slices, light absorption characteristics of the dyeing partitions are measured through a photometer, and dyeing characteristics are determined based on the light absorption characteristics and the color gradient vectors; obtaining a dyeing image after dyeing the lymph tissue section, extracting deep features of the dyeing partitions from the dyeing image, and determining a dyeing loss value when dyeing the dyeing partitions based on the deep features and the dyeing features; and based on the dyeing loss value, carrying out self-adaptive adjustment on the dyeing agent concentration of each dyeing zone. By adopting the scheme provided by the invention, optimal adjustment on the concentration of the coloring agent in the sample dyeing process can be realized based on the characteristic difference of the cell tissues at different parts.

The invention discloses a biomarker for predicting the prognosis condition of sepsis and application, and belongs to the technical field of biology. The biomarkers comprise a ratio of neutrophils to lymphocytes, a ratio of platelets to lymphocytes, a ratio of monocytes to lymphocytes, a ratio of leukocytes to lymphocytes, a system inflammatory response index and a peripheral inflammatory value. According to the method, the ratio of neutrophil to lymphocyte, the ratio of platelet to lymphocyte, the ratio of mononuclear cell to lymphocyte, the ratio of leukocyte to lymphocyte, a systemic inflammatory response index and a peripheral inflammatory value are utilized to carry out accurate prognosis risk stratification on the sepsis patient, and prognosis survival risk prediction is carried out on the sepsis patient; the accuracy and timeliness of prognosis evaluation of sepsis patients are remarkably improved, a reliable guidance basis is provided for clinical decision making, and the method has important clinical application value and popularization significance.

The invention discloses a key effect and a targeted intervention strategy of YTHDF1 in regulation and control of a hepatocellular carcinoma immunosuppression microenvironment. In the tumor-associated fibroblasts, YTHDF1 enhances the translation efficiency of OTUD5 mRNA through an m6A dependency mechanism, an up-regulated deubiquitination enzyme OTUD5 is directly combined with a tryptophan metabolic rate-limiting enzyme IDO1, ubiquitination degradation of the tryptophan metabolic rate-limiting enzyme IDO1 is inhibited, tryptophan is further driven to catabolism to generate kynurenine, regulatory T cell differentiation is promoted, and an immunosuppression microenvironment is formed. Spatial transcriptomics shows that YTHDF1 + CAFs and Tregs are significantly co-localized in tumor tissues and have metabolic interaction. Based on artificial intelligence virtual screening, it is found that a natural compound hesperidin can be specifically combined with a YTH structural domain of YTHDF1, an OTUD5-IDO1 signal axis mediated by the natural compound hesperidin is blocked, and the KYN level is remarkably reduced. Animal experiments prove that the tumor inhibition rate of combined treatment of hesperidin and anti-PD-1 is increased by 40% or above compared with that of a single drug group, and synergistic interaction is achieved by inhibiting Tregs infiltration and enhancing the activity of cytotoxic T lymphocytes.

The present invention relates to a system and a method for measuring and analyzing minimal residual disease (MRD) in pediatric B-cell precursor acute lymphoblastic leukemia (B-ALL) using multiparameter flow cytometry (MPFC). The invention finds application in clinical diagnostics and hematology-oncology for quantifying MRD in B-ALL patients with high sensitivity and specificity, needed for risk stratification, monitoring treatment response, and informing therapeutic decisions. The system comprises interconnected subsystems including an acquisition subsystem with an MPFC instrument, a control and file generation subsystem, and an analytical subsystem. The analytical subsystem incorporates modules for sequential data reduction, automated data cleaning, automated unsupervised data clustering, and interactive cluster analysis. Key advantages include high MRD detection sensitivity (e.g., 10⁻⁵ or 0.001%) and high specificity, without reliance on reference samples or supervised machine learning models, making it applicable in laboratories with different measuring equipment and using different panels of antibodies for identification of leukemic cells.

The invention discloses an application of a pyrrosia lingua aqueous extract in preparation of a medicine for preventing and treating radioactive intestinal injury. Radioactive intestinal injury is a common complication of ionizing radiation, and has main pathological characteristics of intestinal mucosal barrier destruction, excessive release of inflammatory factors, increase of oxidative stress level and hematopoiesis and immune function inhibition. At present, no effective and safe prevention and treatment medicine is available. It is found for the first time that the pyrrosia lingua aqueous extract can inhibit expression (IL-6, TNF-alpha and IL-1beta) of inflammatory factors of radiation-induced MODE-K cells and relieve the oxidative stress level (malondialdehyde (MDA) is reduced, and the content of superoxide dismutase (SOD) and glutathione (GSH) is increased). In animal experiments, the pyrrosia lingua aqueous extract can reduce the levels of TNF-alpha and IL-1beta inflammatory factors in serum of irradiated mice and improve oxidative stress disorders such as MDA increase, SOD and GSH decrease and the like; the reduction of leukocytes and lymphocytes is relieved; the length of intestinal villus is promoted and recovered; the proportion of Ki67 positive cells in a crypt region is increased, so that the regeneration capacity of intestinal epithelial cells is enhanced. The pyrrosia lingua aqueous extract disclosed by the invention provides an experimental basis and an application prospect for developing a novel medicine for preventing and treating the radioactive intestinal injury.

The application discloses a use of Ejiao Qianggu oral liquid in regulating immunity, and particularly relates to an improving effect of the Ejiao Qianggu oral liquid on an immune system, which is realized by the following aspects. On one hand, the Ejiao Qianggu oral liquid promotes proliferation and transformation (mainly early T lymphocytes and part of B lymphocytes) and active functions of spleen lymphocytes; on the other hand, the Ejiao Qianggu oral liquid improves phagocytosis of macrophages. The Ejiao Qianggu oral liquid has the following characteristics: firstly, the Ejiao Qianggu oral liquid acts on early lymphocyte maturation, and has no significant effect on proliferation of peripheral blood lymphocytes; secondly, the Ejiao Qianggu oral liquid can significantly act on immune target organs, thymus and spleen tissues, and does not excessively stimulate the spleen, unlike positive drugs such as colony stimulating factor which can cause significant edema of the spleen; and thirdly, the Ejiao Qianggu oral liquid has a significant recovery effect on body weight, white blood cells, lymphocytes, red blood cells and hemoglobin in blood of patients with low immunity.

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 invention discloses preparation of a methoxyl derivative and application of the methoxyl derivative in pharmacy. The methoxy derivative as shown in the formula I has good anti-tumor activity, and the anti-tumor effect is effectively achieved through the growth inhibition and killing effect on tumor cells. The methoxyl derivative not only can inhibit the growth of CT26 transplanted tumors, but also can promote the activation and infiltration of lymphocytes in an in-vivo tumor microenvironment. Meanwhile, the compound also has a remarkable inhibiting effect on the growth of mouse colon cancer CT26 cell strains in vitro.

The disclosure provides a chimeric antigen receptor (CAR) polypeptide having an antigen binding domain comprising an extracellular lectin which specifically binds to glycoproteins expressed on the surface of target cells. Also provided herein are engineered lymphocytes expressing the CAR polypeptide, a nucleic acid molecule encoding the CAR polypeptide, and methods of treating cancer.

The utility model belongs to the technical field of medical instruments, and particularly relates to a rapid lymphocyte separating tube with adjustable volume, which comprises a tube body, a separating device, a threaded section and a rotary moving rod, the threaded section is arranged on the inner wall of the middle of the tube body, the separating device is connected inside the tube body in a sliding manner through the threaded section, and the rotary moving rod is arranged on the inner wall of the middle of the tube body. The separating device is provided with a central separating hole for a sample to pass through during centrifugation, and the rotary moving rod is clamped with the separating device through the central separating hole. According to the device, the positions of the partition plates can be adjusted according to blood of different volumes, so that the requirement of rapidly separating lymphocytes from the blood of different volumes is met, and time and resources are saved.

The present disclosure relates to an apparatus including one or more processors configured to receive a digitized image of a region of tissue demonstrating a disease, and containing cellular structures represented in the digitized image, each of the cellular structures being associated with a cell category of a plurality of cell categories; select a cellular structure of the cellular structures based on the cell category for the cellular structure; for the cellular structure selected, compute a set of contextual features; assign, based on the set of contextual features, the cellular structure to at least one cluster of a plurality of clusters; compute cluster features, the cluster features describing characteristics of the at least one cluster of the plurality of clusters; and generate a prediction that describes a pathologic or phenotypic state of the disease based, at least in part, on the cluster features and / or the set of contextual features.

The utility model provides a device convenient for storing donor lymphocytes, and relates to the field of medical instruments. The device comprises a positioning support frame which is sequentially provided with a plurality of storage spaces at intervals in the direction from the top to the bottom; the storage boxes are used for placing and storing donor lymphocyte test tubes, the number of the storage boxes is equal to that of the storage spaces, and the storage boxes are respectively matched with the storage spaces one by one; any storage box is matched with the matched storage space in an inserted mode, and the insertion ports of the multiple storage spaces are located on the same side of the positioning supporting frame. The limiting rod is detachably matched with the positioning support frame, simultaneously penetrates through the insertion ports of the plurality of storage spaces and is used for limiting the plurality of storage boxes in the plurality of storage spaces respectively; and the lifting rod is arranged at the top of the positioning support frame. According to the device, the test tube storage stability is improved, shaking and toppling during transferring are avoided, and the sample damage and pollution risk is reduced.

The present invention discloses the application of CD40 antibody and LPS co-stimulated genetically modified B cells in the treatment of cancer, belonging to the field of biotechnology. First, the present invention discovers that B cells co-stimulated by LPS and anti-CD40 antibody can be used as cell vectors for gene therapy, continuously expressing dFv-LDP protein in vivo to treat cancer. The present invention discovers that B lymphocytes can continuously express dFv-LDP protein for a long time, solves the problem of too rapid reduction of the blood drug concentration of scFv protein to achieve a better therapeutic effect than directly injecting dFv-LDP protein, and at the same time can reduce the economic burden on patients caused by multiple injections of scFv protein.

The invention belongs to the technical field of biological medicines, and particularly relates to application of a cancer suppressor gene SLC26A11 in hyperleukocyte acute B lymphocytic leukemia. The invention discloses an application of a cancer suppressor gene SLC26A11 as a specific molecular marker in preparation of induction treatment reaction, prognosis and risk assessment of high leukocyte acute B lymphocytic leukemia of children, and an application in improvement of sensitivity of chemotherapeutic drugs for high leukocyte acute B lymphocytic leukemia of children. The SLC26A11 is used as a potential target, so that a personalized treatment scheme is provided for HALL patients, the toxic and side effects of chemotherapeutic drugs are reduced, and the treatment effect is improved.

A method for reprogramming native CD4+ T-cells is provided. The method comprises incubating the CD4+ T-cells with a Class 1 HDAC inhibitor for a period of time sufficient to increase cytotoxicity of the CD4+ T-cells in comparison to the cytotoxicity of native CD4+ T-cells. The method may be utilized to prepare cytotoxic tumor infiltrating CD4+ T-cells for use to treat cancer, including MHC-I deficient cancers.

The invention provides a lung cancer microenvironment ecological characteristic detection and curative effect evaluation system, and relates to the technical field of lung cancer prognosis evaluation, and the system comprises a reading module which is used for reading slice information of a subject; the boundary construction module is used for constructing a region boundary according to the tumor region in the slice information; identifying tumor infiltrating lymphocytes (TILs for short) from the slice information, and determining the distribution type of the tumor infiltrating lymphocytes in combination with the distribution characteristics and the region boundary of the tumor infiltrating lymphocytes; the method comprises the following steps of: obtaining slice information, identifying a three-level lymphatic structure (TLS for short) from the slice information, and determining a distribution type of the three-level lymphatic structure in combination with distribution characteristics and a region boundary of the three-level lymphatic structure; and the evaluation module is used for performing prognosis effect prediction on the subject based on the distribution type of tumor infiltration lymphocytes and the distribution type of the three-level lymphatic structure, deeply analyzing the immune condition of a tumor micro-environment (TME for short), and improving the accuracy of prognosis evaluation.

The invention discloses a fracture risk prediction method and system, and relates to the technical field of health management. According to the prediction method, serious sarcopenia is selected to diagnose and assess the sarcopenia state, the ratio of monocytes to lymphocytes reflects the immune inflammation level, the prediction model is constructed in combination with the femoral neck bone mineral density T value, and the fracture risk influence factors are comprehensively covered; and the risk identification capability on special high-risk groups with sarcopenia, immune dysfunction and the like is effectively improved. And secondly, only three target independent variables are selected, and the three target independent variables are indexes which can be directly obtained or simply calculated in clinical routine examination, so that the data collection difficulty is greatly reduced. Meanwhile, the prediction model is visualized through a column diagram, complex calculation is not needed, a clinician can quickly inquire the fracture risk score through the actual value of the target subject, and the method is suitable for being efficiently applied to conventional outpatient service, hospitalization and other scenes.

This invention belongs to the field of biomedical technology, specifically relating to a culture reagent composition and method for organoids from hematologic malignancies. The invention first provides a reagent composition for culturing organoids from hematologic malignancies, including acute lymphoblastic leukemia or acute myeloid leukemia; the reagent composition includes a bone marrow microenvironment mimicking matrix reagent and a specific culture medium. Using the reagent composition of this invention, hematologic malignancies can be cultured efficiently with high survival rates. Furthermore, the bone marrow microenvironment mimicking matrix component used in this invention, compared to the commonly used Matrigel matrix in the field, allows for more accurate phenotypic differentiation of hematologic malignancies.

The invention provides systems and methods for determining and predicting the effect of providing a population of tumor infiltrating lymphocytes (TILs) on a condition associated with an entity, for example the effect of providing a population of tumor infiltrating lymphocytes (TILs) on a subject having cancer. The systems and methods rely on acquiring a computer readable analytical signature from a sample of the entity, obtaining a trained model output value for the entity by inputting the computer readable analytical signature into a tier trained model panel, and classifying the entity based upon the trained model output value with a time-to-event class in an enumerated set of time-to-event classes, each of whom is associated with a different effect of providing a population of TILs to the entity.The invention provides methods of treating cancer in a patient by administering a therapeutically effective population of TILs to the patient, which is at the same determined to be likely to benefit from the administration of TILs comparative to other cancer patients that have been administered TILs. Such methods of treatment include obtaining from the patient a tumor fragment, contacting the tumor fragment with one or more cell culture mediums, thereby performing one or more expansions of population of TILs existing in the tumor, and producing one or more subsequent populations of TILs. The invention also provides methods of treating cancer in a patient exhibiting an increased or decreased level of expression of various biological markers.

The present application provides chimeric anti-CD27 antibody molecules and encoding nucleic acids and expression vectors thereof. The anti-CD27 antibody molecules of the present application can specifically bind to CD27 and have effects of stimulating lymphocyte proliferation, activating lymphocytes, etc.

The invention relates to the technical field of biological medicines, in particular to a maggot alcohol extract for improving chemotherapy immune injury, a preparation method of the maggot alcohol extract and application of the maggot alcohol extract in preparation of medicines, health-care products or functional foods for preventing or treating immune injury caused by chemotherapy medicines. It is found for the first time that the maggot alcohol extract has a remarkable protection effect on immune injury caused by chemotherapeutic drugs such as cyclophosphamide, the number of leukocytes and lymphocytes can be effectively increased, and immune organ atrophy is relieved. The maggot alcohol extract disclosed by the invention can be used for preparing medicines, health care products or functional foods for preventing or treating immune injury caused by chemotherapy, has the characteristics of multiple target spots, high efficiency and low toxicity, is simple and stable in preparation process, and has good development and application prospects.