14 results about "B-cell activation" patented technology

The invention discloses a neutralizing nucleic acid aptamer for targeted inhibition of a B cell activating factor and application of the neutralizing nucleic acid aptamer in treatment of systemic lupus erythematosus. The neutralizing aptamer disclosed by the invention can be used for efficiently inhibiting the combination of BAFF and specific receptors on a B cell membrane, including a BAFF receptor (BAFF-R), a human calcium regulatory cyclophilin ligand interaction molecule (TACI) and a B cell maturation antigen (BCMA), so that the proportion of plasma cells, plasma mother cells and hair growth center B cells is reduced, and finally, the generation and secretion of autoantibodies are reduced; the compound has a targeted therapeutic effect on systemic lupus erythematosus. Compared with an existing biological agent for neutralizing BAFF, the neutralizing nucleic acid aptamer has the advantages of being high in specificity, high in affinity, easy to synthesize, low in immunogenicity, low in cost, capable of being designed and programmed and the like, is a potential novel nucleic acid preparation for SLE targeted therapy, and has a good clinical transformation application prospect.

The present application relates to the role of UCK1 in promoting the sensitization of colorectal cancer treatment. The present application discloses the key role of UCK1 in the treatment of colorectal cancer. Clinical samples show that the expression of UCK1 in tumor tissues is reduced, and its low expression is related to chemotherapy resistance and poor prognosis. Studies have shown that UCK1 enhances the efficacy of oxaliplatin (OXA) by regulating metabolic pathways, and promotes B cell activation, thereby recruiting CD8 + T cells, and strengthens anti-tumor immunity. UCK1 overexpression can significantly improve OXA sensitivity and produce a synergistic effect with anti-PD-1 therapy. The present application proposes a new strategy centered on activating UCK1, providing a theoretical basis and application prospect for improving the response of colorectal cancer chemotherapy and immunotherapy.

Described herein are compositions and methods of use thereof for reducing inhibiting B cell activation, B cell proliferation, the production of pathologic, autoimmune or interfering antibodies; and / or for eliciting humoral suppression and / or B cell tolerance in a subject in need thereof by contacting immune cells of the subject or donor immune cells in vivo and / or ex vivo with a composition comprising a Butyrophilin, optionally Butyrophilin A2, or a conjugate or fusion protein comprising said Butyrophilin. The methods include the use of butyrophilin A2 (BTN2A2), a BTN2A2 fragment thereof, a BTN2A2- related isoform, or a BTN2A2-related isoform fragment, or conjugates, and fusion polypeptides containing, preferably which comprise an Fc region comprising one or more mutations which reduce FcR binding and / or which suppress FcRN mediated clearance.

The invention relates to the field of biological medicines, and discloses application of an OGG1 micromolecule agonist in preparation of a medicine for treating liver inflammatory diseases. According to the micromolecule TH10785, by activating the beta, delta-lyase activity of DNA repair enzyme OGG1, the oxidized DNA repair capacity is remarkably enhanced, ROS accumulation in liver cells is reduced, NF-kappa B signal channel activation and proinflammatory factor release are inhibited, and therefore liver inflammation and fibrosis are effectively relieved. Meanwhile, the medicine can inhibit the activation of B cells and the formation of plasma cells, finally reduces the generation of autoimmune antibodies, and improves the immune imbalance state of autoimmune hepatitis. The invention provides an innovative treatment strategy based on OGG1 enzyme function amplification, and a new pharmacological approach is provided for treatment of chronic liver diseases and immunological liver injury.

Recombinant receptors with a binding domain that binds B cell activation factor receptor (BAFF-R) are disclosed. Recombinant receptors include chimeric antigen receptors (CAR) having an anti-BAFF-R binding domain, a transmembrane domain, a CD3ζ / 4-1BB intracellular signaling domain, and a spacer. Methods and systems to treat BAFF-R-expressing cancers, such as mantle cell lymphoma (MCL), multiple myeloma (MM), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL), are also provided. The recombinant receptors disclosed herein can bind and elicit cytotoxic effects even in low antigen density conditions.

Disclosed herein is a method of treating a tumor in a subject that involves a) treating the tumor with an effective amount of radiotherapy: b) treating the subject with an effective amount of a B cell agonist: and c) administering to the subject a 4-1BB agonist. In some embodiments. the 4-1BB agonist is an isolated monoclonal antibody. or antigen binding portion thereof, that specifically binds human CD137 (4-1BB).

The invention relates to the field of biological medicine, and relates to application of an interferon receptor 1 monoclonal antibody in preparation of a medicine for treating neuromyelitis optica pedigree diseases and a medicine composition. The antibody regulates immune response by inhibiting abnormal activation of an I-type interferon signal channel and down-regulating interferon stimulation gene expression, so that central nervous system inflammation and demyelination injury are relieved. The humanized IFNAR1 monoclonal antibody is independently used; the compound is combined with a B cell targeting drug to synergistically inhibit B cell activation and antibody secretion; and a bispecific antibody targeting IFNAR1 and a transferrin receptor is constructed, so that the ability of the drug to pass through the blood brain barrier is enhanced, and the concentration of the drug in the brain is improved. In-vivo and in-vitro experiments prove that the treatment scheme can effectively reduce the size of the focus of the NMOSD model and improve the neurological function, and a new precise treatment strategy is provided for AQP4 antibody positive patients.

An antibody specifically binding to BDCA2 and a BDCA2-TACI antibody fusion protein. The antibody fusion protein contains the following elements which are fused together: (a) an antibody or antigen-binding fragment thereof that specifically binds to BDCA2; and (b) TACI or an active fragment thereof. The antibody and antibody fusion protein can inhibit pDC activity, reduce IFNα secretion, inhibit cell inflammatory responses, neutralize factors such as BAFF and APRIL released by monocytes, etc., and reduce B cell activation.

The invention relates to the technical field of biological medicines, and particularly discloses an organoid simulating a lymphatic epithelial tissue structure and application thereof. The organoid comprises an immune micro-region capable of supporting B cell activation, somatic mutation and / or the formation of a hair growth center-like structure, and the organoid is derived from a cell population of lymph-related tissue. According to the method, a Transwell three-dimensional culture system supported by a low-concentration matrix is adopted, and optimized culture conditions are combined, so that B cells are promoted to form a hair growth center-like structure in an organoid. The method can be applied to mucosal immune mechanism research, vaccine or immunologic adjuvant evaluation, immunomodulatory drug screening, antibody discovery and screening, hair growth center related immune response research and the like.

The application discloses application of monoclonal antibody 2F5 in autoimmune diseases and regulation of B cells, wherein the monoclonal antibody 2F5 is obtained from peripheral blood of SLE, and it is first proved that the monoclonal antibody 2F5 can promote B cell proliferation, activation and differentiation through primary cell and cell line experiment models. The antibody provided by the application is completely humanized, has clear targeting, can well simulate a blood microenvironment of high-titer autoantibodies in peripheral blood of an autoimmune disease patient, is an ideal tool for understanding biological functions of the autoantibodies and studying regulation of B cell activation and differentiation by the autoantibodies, and is helpful to deepen understanding of mechanisms of immune disorders, to make it possible to treat immunopathological diseases caused by abnormal differentiation of B cells, and to lay an important foundation for developing a new target for treating autoimmune diseases and tumors by targeting pathogenic B cells.

The present application relates to the technical field of biological medicine, and discloses an LDLR intervention adjuvant for promoting antibody production and enhancing vaccine effect and application thereof. The LDLR intervention adjuvant can promote B cell activation and generation of antigen-specific antibodies by down-regulating the expression level of LDLR. The LDLR intervention adjuvant includes, for example, ShRNA or SiRNA for knocking down LDLR gene expression, or PCSK9 functional peptide segments for specifically targeting LDLR protein degradation. The present application proposes a new method for promoting B cell function, i.e. knocking down the expression level of the metabolism-related receptor LDLR, which can effectively promote B cell activation and thus increase the production of specific antibodies.

Disclosed are a Bruton's tyrosine kinase and a mutant degrader thereof, or a stereoisomer thereof, or a stereoisomer mixture thereof or a pharmaceutically acceptable salt thereof, and an application thereof in the preparation of a drug for treating diseases, disorders or conditions that would benefit from the degradation of the Bruton's tyrosine kinase and the mutant thereof. The compound of the present invention can degrade BTK protein, can degrade BTKC481S protein, has an anti-proliferation inhibiting effect on tumor cell strains Mino and OCI-LY10, shows good anti-tumor activity in an OCI-LY10 subcutaneous transplantation tumor model, has an inhibiting effect on B cell activation, and can be applied to B cell or plasma cell proliferative diseases and autoimmune diseases. The compound of the present invention has good oral absorption properties, and can be applied to oral treatment of human or animal B cell or plasma cell proliferative diseases and autoimmune diseases.

Recombinant receptors with a binding domain that binds B cell activation factor receptor (BAFF-R) are disclosed. Recombinant receptors include chimeric antigen receptors (CAR) having an anti-BAFF-R binding domain, a transmembrane domain, a CD3ζ / 4-1BB intracellular signaling domain, and a spacer. Methods and systems to treat BAFF-R-expressing cancers, such as mantle cell lymphoma (MCL), multiple myeloma (MM), acute lymphoblastic leukemia (ALL), and diffuse large B-cell lymphoma (DLBCL), are also provided. The recombinant receptors disclosed herein can bind and elicit cytotoxic effects even in low antigen density conditions.

This invention discloses a degrading agent for Bruton's tyrosine kinase and its mutants, or its stereoisomers, or mixtures thereof, or pharmaceutically acceptable salts thereof, as well as the therapeutic application of drugs for treating diseases, disorders, or conditions caused by the degradation of Bruton's tyrosine kinase and its mutants. [Solution] The compounds of the present invention can degrade BTK protein and BTKC481S protein, have antiproliferative inhibitory activity against Mino and OCI-LY10 tumor cell lines, show good antitumor activity in the OCI-LY10 subcutaneous graft model, have inhibitory activity against B cell activation, and can be applied to the treatment of B cell or plasma cell proliferative disorders and autoimmune diseases. The compounds of the present invention have relatively good oral absorption and can be applied to the oral treatment of B cell or plasma cell proliferative disorders and autoimmune diseases in humans or animals.