42 results about "Immune Cell Function" patented technology

This disclosure describes an artificial expression construct containing a PD1:cytokine chimeric transgene under the control of an inducible promoter. The artificial expression construct of this disclosure can be used to enhance the function of immune cells (e.g., CAR-T cells) that have recombinant receptors. The inducible PD1:cytokine chimeric transgene disclosed herein enhances the potency of immune cells (e.g., CAR-T cells) that have recombinant receptors, thereby enhancing killing, proliferation of immune cells, and / or cytokine production.

Fusion proteins that bind to human CD8α, human CDSβ, or human PD1 and comprise mutant IL-2 polypeptides, as well as polynucleotides, host cells, compositions, and methods of use thereof, are provided herein. The present disclosure describes, inter alia, mutant IL-2 polypeptides having one, two, or more, or three, or more amino acid substitutions (i.e., mutations) relative to the wild-type mature IL-2 amino acid sequence, e.g., as depicted in Figure 1A (SEQ ID NO: 1) and Figure 2.

The invention provides an immune senescence detection marker Granzyme B, an immune senescence regulation and control target BHLHE40 and application, and belongs to the technical field of biological medicine. The invention discloses the continuous up-regulation characteristic of the GZMB in the senescence process of the primate immune system for the first time, defines the consistent expression trend of the GZMB in various immune tissues, and determines that the GZMB can be used as a reliable molecular marker for reflecting the overall immune senescence state. The invention also discloses a key regulatory pathway for immune aging, and finds that the GZMB can activate an NF-kappa B signal pathway, up-regulate inflammation and aging related genes such as CDKN1A, NFKBIA and S100A4, and promote functional degradation of immune cells; it is identified that the transcription factor BHLHE40 is a key upstream regulation factor of GZMB, expression of GZMB and downstream senescence genes can be remarkably reduced by knocking down BHLHE40, and the core effect of the BHLHE40-GZMB pathway in immune senescence is clarified.

The invention belongs to the technical field of biological medicines, and particularly discloses application of aspirin in enhancing the curative effect of tumor infiltrating lymphocyte on treating liver cancer. The invention discloses application of aspirin in preparation of a medicine for enhancing the curative effect of tumor infiltrating lymphocyte on hepatocellular carcinoma. The invention discloses an application of aspirin in enhancing the curative effect of tumor infiltrating lymphocyte on treating liver cancer, the aspirin overcomes the problem of drug resistance of TIL therapy in HCC by adjusting the immune cell function in a tumor microenvironment, and the treatment effect is improved.

The invention discloses a broncholung lavage fluid composition for treating non-small cell lung cancer, and relates to the technical field of cancer treatment. The preparation method of the bronchus lung lavage fluid composition for treating the non-small cell lung cancer comprises the following steps: S1, performing metagenome sequencing on a BALF sample, S2, grouping by R / NR based on differential strains obtained in S1 to obtain core bacteria, performing single-strain Kaplan-Meier survival analysis on the strains, and determining the survival rate of the single-strain Kaplan-Meier to obtain the bronchus lung lavage fluid composition for treating the non-small cell lung cancer. Finally, seven key microorganisms, namely bronchopulmonary lavage fluid combinations, which are remarkably related to immunotherapy PFS are locked; s3, determining the relationship between the seven key BALF bacteria and the existing immune therapeutic effect marker; and S4, verifying the generation conditions of IL6, IL8 and RANTES cytokines promoted by the seven strains through an in-vitro cell experiment, and revealing the activation and enhancement effects of the seven strains on immune cell functions. According to the invention, the immunotherapy effect of the non-small cell lung cancer patient can be promoted to be improved by combining a plurality of beneficial specific microorganisms in an airway administration mode. In conclusion, the method has a good application prospect.

The present disclosure relates to the field of cell therapy, and more specifically, to improving CAR and / or TCR function through improvement of cytokine signaling. Disclosed are embodiments of a membrane bound interleukin 15 (IL-15)-IL-15Ralpha sushi domain chimeric receptor. The chimeric receptor may comprise a FAS transmembrane domain or an IL-7 transmembrane domain. Different embodiments of the chimeric receptor have different polypeptide lengths between the IL-15 region and the transmembrane domain.

The present application relates to the technical field of biological medicine, and particularly relates to application of fullerenol in preparation of tumor prevention or treatment drugs for inducing trained immunity. The present application finds that fullerenol can induce formation of trained immunity, activate immune reprogramming of bone marrow hematopoietic stem cells, produce long-term pro-inflammatory phenotype, form persistent immune memory, and further enhance functions of innate immune cells. It is verified by experiments that fullerenol can significantly inhibit tumor growth in an animal model without obvious systemic toxicity; epigenetic remodeling of bone marrow hematopoietic stem cells can be sustained for several weeks to several months, and has long-acting anti-recurrence potential. In addition, trained immunity induced by fullerenol can be used for immune regulation of various solid tumors, and fullerenol is simple in synthesis, can be produced on a large scale, has excellent biocompatibility and stability. Therefore, the present application has wide application prospect.

The invention provides an oral liquid based on algal oil-curcumin synergistic anti-inflammation and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations. The oral liquid comprises the following raw materials: an anti-inflammatory agent (consisting of algae oil and curcumin), a traditional Chinese medicine extract (consisting of a herba houttuyniae extract and an Indian kalimeris herb extract), phospholipid, fructo-oligosaccharide, an antioxidant, a stabilizer (consisting of Arabic gum and hydroxypropyl-beta-cyclodextrin) and a flavoring agent. Experimental results show that the anti-inflammatory oral liquid is high in stability, and the content of inflammatory factors in mice with LPS-induced chronic inflammation can be remarkably reduced. The oral liquid can relieve chronic inflammation symptoms by regulating immune cell functions, blocking inflammation signal channels and other multi-target mechanisms, is high in safety after being used for a long time, does not have obvious adverse reaction, and provides a new choice for clinical treatment of chronic inflammatory diseases.

The invention relates to a piezoelectric nano-material with ultrasonic responsiveness, which is a PVP (Polyvinyl Pyrrolidone) modified bismuth oxyiodate nano-sheet, the particle size is 100-200 nm, and a surface electric field can be generated under the ultrasonic action. The piezoelectric nano material can hyperpolarize the potential of a T cell membrane and inhibit an ion channel Kv1.3 regulated and controlled by the membrane potential, so that Th17 cell differentiation is reduced, and joint inflammation is relieved; the piezoelectric nano material is further prepared into a joint injection preparation, and the joint injection preparation can be combined with ultrasonic irradiation to be applied to treatment of rheumatoid arthritis. According to the invention, the piezoelectric nano material is successfully applied to immune microenvironment regulation and control of rheumatoid arthritis for the first time, and the product and technology blank in the field of'precisely regulating and controlling immune cell functions by using physical signals to treat autoimmune diseases' is filled.

The methods and compositions disclosed herein relate to the field of cell therapy, and more specifically, to improving CAR and / or TCR function through improvement of the tumor microenvironment via improvement in cytokine signaling. Methods of treating a cancer in a patient are disclosed comprising administering to the patient immune cells expressing a chimeric antigen receptor or T-cell receptor and a membrane bound IL-18. Further disclosed are nucleic acids which encode a membrane bound IL-18 and methods for culturing cells expressing such nucleic acids.

The application relates to modified immune effector cells with enhanced immune cell function, as well as related pharmaceutical compositions. The application further relates to methods for generating the modified immune effector cell and methods for using the modified immune effector cell for treatment of diseases (e g., adoptive cell therapy).

The invention relates to an application of a CXCL13 + CD8 + T cell subset in preparation of a product for predicting prognosis of a melanoma patient, and the CXCL13 + CD8 + T cell subset is used as an analysis target to prepare a reagent for analyzing immune cell functions. Wherein the CXCL13 < + > CD8 < + > T cell subset refers to a CD8 < + > T cell subset capable of releasing a CXCL13 signal. Compared with the prior art, the research shows that by analyzing the expression level of effector molecules and immune checkpoint molecules in a tumor microenvironment and the density of a three-level lymph structure, the prognosis of a tumor patient can be more accurately predicted, and the reactivity of tumors to immunotherapy can be predicted; at present, a report for reflecting immune characteristics of melanoma by using the CXCL13 + CD8 + T cell subset as a biomarker is not found. The infiltration level of CXCL13 + CD8 + T cells in tumor tissues is quantitatively evaluated through flow cytometry, and more accurate and sensitive indexes are provided for prognosis evaluation of melanoma and liver cancer patients.

The present disclosure provides polypeptide constructs that, when exposed to sufficient levels of ATP, cause them to assemble into dimers or higher order complexes (e.g., trimers, tetramers, etc.), thereby acting as immune cell function agonists. The constructs can also be conjugated to one or more therapeutic, chemotherapeutic, or labeling agents. The complexes of the constructs are capable of stimulating immune cells (e.g., cytotoxic CD8+ T cells and / or NK cells) that function to promote an anti-tumor immune response, and delivering the conjugated agent to the tumor microenvironment. The constructs can be used as anti-cancer / therapeutic agents for the treatment of solid tumors with elevated ATP levels.

The present application relates to the technical field of database construction, and particularly relates to a method and system for constructing a reproductive medicine database. The method comprises the following steps: obtaining a patient biological tissue sample; obtaining reproductive endocrine hormone data, embryo morphology parameter data, immune cell function data and genomic variation data of the patient biological tissue sample; performing time series analysis and processing on hormone fluctuation patterns according to the reproductive endocrine hormone data to obtain endocrine dynamic characteristic data; performing image recognition processing based on light coherence superposition characteristics on the embryo morphology parameter data, and performing embryo development potential evaluation to obtain embryo development potential data; and performing hierarchical clustering processing on patient individual heterogeneity according to the immune cell function data and the genomic variation data to obtain patient immune-heredity typing data. The present application realizes standardization of data acquisition through quantum dot sensing technology and a multi-channel microfluidic chip, and solves the problem of heterogeneity of data sources.

This invention provides a method for generating immune cells with enhanced function. [Solution] A method for enhancing the function of immune cells is disclosed herein, comprising modifying immune cells to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1, and TGFBR2. A method also disclosed herein, comprising modifying stem cells or progenitor cells that can differentiate into immune cells to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1, and TGFBR2. The use of immune cells or stem cells produced by this method, and immune cells in therapeutic treatments, is also disclosed herein.

The present disclosure relates to methods of coupling antic-cancer agents and anti-cancer treatments to improve the efficacy of the overall treatment. The anti-cancer agent reduces stroma in the tumor microenvironment, in part by killing stroma producing cells such as TAFs and TAMs. Reduction of tumor stroma not only improves immune cell function, including immune cells administered in a second treatment, but also allows allowing other anti-cancer treatments to better access to tumor cells.

The present invention provides a multispecific polypeptide construct comprising: (a) one or more antigen targeting domains that bind to one or more tumor-associated antigens; and (b) one or more NK cell targeting domains, wherein binding to NK cells may stimulate and / or inhibit innate immune cell function. Also disclosed are antigen binding proteins or antigen binding fragments thereof; a nucleic acid sequence; a carrier; a host cell; methods of making multispecific polypeptide constructs or antibodies; methods of screening and / or identifying multispecific polypeptide constructs or antibodies as disclosed herein; a pharmaceutical composition; and methods of treating cancer.

The invention relates to the field of neurology, neurobiology, and neurological disorders. The invention relates to a pharmaceutical combination comprising a colony-stimulating factor 1 receptor (CSFR1R) inhibitor and a bone marrow cell population for use in the treatment of central nervous system (CNS) diseases. The invention further relates to an ex vivo method for depleting dysfunctional and / or mutant microglia and / or CNS-associated macrophages (CAM), the method comprising providing a population of cells comprising myeloid cells and treating said cells with an CSF1R inhibitor of central nervous system (CNS)-associated myeloid cells, thereby depleting dysfunctional and / or mutant microglia. The invention relates to a cell population according to the ex vivo method. The invention further relates to a pharmaceutical composition comprising the CSF1R inhibitor according to the present invention for use in the treatment or prevention of a medical condition induced by dysfunction of immune cells in a central nervous system (CNS), additionally comprising a pharmaceutically acceptable carrier.

The invention relates to the technical field of edible mushroom polysaccharide extraction, in particular to agrocybe cylindracea beta-1, 3-glucan as well as a preparation method and application thereof. The preparation method comprises the following steps: adding agrocybe cylindracea sporocarp and water, extracting at 80-90 DEG C for 2-3 hours, and extracting for 2-3 times; after extraction, combining the two filtrates to obtain an extracting solution I; drying the residues, adding the dried residues into an alkaline solution, extracting for 2-3 times at 70-90 DEG C, combining the two extracting solutions, and adjusting the pH value to be neutral to obtain an extracting solution II; combining the extracting solution I and the extracting solution II to obtain a total extracting solution; carrying out micro-filtration membrane treatment on the total extracting solution, collecting a non-permeated solution, freeze-drying, re-dissolving in water, adding an ethanol solution with the concentration of 90-95%, and carrying out alcohol precipitation treatment; and collecting the precipitate, and freeze-drying to obtain the agrocybe cylindracea beta-1, 3-glucan. The agrocybe cylindracea beta-1, 3-glucan has the advantages that the agrocybe cylindracea beta-1, 3-glucan can be used for improving the innate immune cell function by training immunity and enhancing the body immunity.

The invention relates to a multiple shRNA combination and application thereof, and belongs to the technical field of biology. The combination comprises a first transcription unit, a second transcription unit and a third transcription unit which are located on the same expression vector and respectively silence three different target genes in a targeted manner. Each transcription unit comprises an RNA (Ribonucleic Acid) polymerase III promoter, an shRNA (Short Hairpin Ribonucleic Acid) coding sequence and a transcription termination signal; and promoters for driving the three transcription units are different from one another and are selected from any three of hU6, mU6, hH1, h7SK, mini-hU6, H1-7SK and hH1-core. According to the technology, simultaneous efficient, stable and lasting silencing of three target genes is realized by avoiding homologous recombination, nucleic acid constructs and expression vectors can be constructed and introduced into immune cells, the functions of the immune cells are effectively enhanced, and the method has application prospects in the fields of treatment of tumors, autoimmune diseases, senescence-related diseases and the like.

The invention provides an anti-human CD226 antibody and application thereof. The antibody comprises a heavy chain variable region and a light chain variable region, the CDR1, the CDR2 and the CDR3 of the heavy chain variable region are amino acid sequences as shown in SEQ ID NO. 1, SEQ ID NO. 2 and SEQ ID NO. 3 respectively; the CDR1, the CDR2 and the CDR3 of the light chain variable region are amino acid sequences as shown in SEQ ID NO. 4, SEQ ID NO. 5 and SEQ ID NO. 6 respectively. The anti-human CD226 antibody disclosed by the invention is detected by using a flow cytometer, and the expression condition of CD226 on cells is judged according to the intensity change of a CD226 fluorescence signal, so that the functional state of human immune cells is judged in an auxiliary manner.

The application relates to modified immune effector cells with enhanced immune cell function, as well as related pharmaceutical compositions. The application further relates to methods for generating the modified immune effector cell and methods for using the modified immune effector cell for treatment of diseases (e.g., adoptive cell therapy).

The present disclosure is directed to leucine zipper-based sorting systems adapted to facilitate the expression and coordination of polypeptide sequences capable of improving the function of CAR T cells. The systems enable the generation of T cells engineered to express multiple combinations of CARs (multi-CAR), safety-switches, switch receptors, and / or cytokines.

The present disclosure is directed to systems for inhibiting NFAT and / or NFkB signaling to improve the function of CAR expressing immune cells, e.g., CAR T cells. The system enables generation of immune cells engineered to express a CAR or multiple combinations of CARs (multi-CAR) and inhibitors of NFAT and / or NFkB signaling.

Provided are modified cells that can alter the glycocalyx of cancer cells. The modified cells include modified lymphocytes that have a one or more plasma membrane-coupled glycocalyx-editing enzymes. The modified lymphocytes include modified immune cells. The modified immune cells include T cells, natural killer cells, macrophages and dendritic cells. The modified immune cells may also express a chimeric antigen receptor. Methods of using the modified cells to alter the glycocalyx of cancer cells, and for cancer therapy, are also provided.

In aspects, a chimeric cytokine receptor (CCR) is provided that comprises (i) a single chain variable fragment (scFv) which specifically binds to an antigen, one or more extracellular interleukin receptor domains, an interleukin receptor transmembrane domain, and an interleukin receptor intracellular domain; and (ii) a single chain variable fragment (scFv) which specifically binds to an antigen, one or more extracellular interleukin receptor common gamma chain (γc) domains, a γc transmembrane domain, and a γc intracellular domain.

The present disclosure relates to methods for producing immune cells with enhanced function. More specifically, disclosed herein is a method for enhancing the function of an immune cell comprising modifying the immune cell to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1, and TGFBR2. Also disclosed herein is a method comprising modifying a stem cell or progenitor cell capable of differentiating into an immune cell to inhibit the function of at least one gene selected from the group consisting of RC3H1, RC3H2, A2AR, FAS, TGFBR1 and TGFBR2. Also disclosed herein are immune cells or stem cells prepared by the methods of the invention and the use of immune cells in therapeutic therapy.

The invention discloses a method for producing high-titer antiserum based on combinatorial immunity, and belongs to the technical field of biological medicine. According to the invention, the TLR agonist and the cell factor are added as immunologic adjuvants, and the TLR agonist activates innate immunity and provides a good immune microenvironment for mRNA-induced antigen-specific immune reaction; the cytokines regulate functions of immune cells and promote recognition and response of the immune cells to mRNA expression antigens. The TLR agonist and the cell factor have a synergistic effect, so that the functions of immune cells can be effectively regulated, proliferation and differentiation of T cells can be promoted, Th1 type immune response can be enhanced, and the immune function of cells can be improved; meanwhile, B cells are promoted to generate high-titer antiserum, and the humoral immune function is enhanced. Compared with pure mRNA immunization, the combined immunization method disclosed by the invention can be used for obtaining antiserum with remarkably improved titer.

The application relates to a breast cancer risk assessment method and related equipment. The method comprises the following steps: obtaining germline genome sequencing data of a target object; the target object is a patient to be evaluated who is positive for breast nodules according to an ultrasonic examination result; inputting the germline genome sequencing data into a breast cancer germline genome evaluation model to obtain a breast cancer germline etiology score result of the target object; determining an immune exhaustion state evaluation result according to immune cell detection data of the target object and immune exhaustion reference information; the immune exhaustion reference information is obtained based on immune exhaustion analysis data of a non-breast cancer population; combining the breast cancer germline etiology score result and the immune exhaustion state evaluation result to obtain a breast cancer risk assessment result of the target object; the immune exhaustion state evaluation result is used for verifying the breast cancer germline etiology score result from the function level of immune cells. The method can effectively improve the accuracy of breast cancer risk assessment.

Disclosed are methods for enhancing the memory-like state of immune cells by treating the cells with itaconate. Enhancing the memory-like state improves immune cell function and persistence. Also disclosed are methods of using the enhanced immune cells for treating cancer and autoimmune diseases.