23 results about "Cell surface molecules" patented technology

An engineered trophoblast that expresses a cell surface molecule that specifically recognizes NKp46, the cell surface molecule comprising at least an antibody targeting NKp46 and a transmembrane domain. The invention discloses a cell culture medium and a method for amplifying NK cells. Compared with unengineered trophoblasts, the engineered trophoblasts are used for activating NK cells, and the amplification capacity of the NK cells and the killing activity of tumor cells can be enhanced.

The invention belongs to the technical field of biological medicines, and particularly discloses application of a CD44 function inhibitor in preparation of a medicine for preventing or relieving radiation liver injury (RILD). Radioactive liver injury is often caused by hepatocellular carcinoma radiotherapy, and specific targeting drugs are lacked clinically. It is revealed for the first time that whether CD44 molecules on the surface of Kuhu cells are highly expressed after radiation, and the CD44 molecules are key hubs for driving RILD; the invention also provides a CD44 function inhibitor which is a specific targeting drug aiming at RILD, and the action mechanism of the CD44 function inhibitor is to effectively block polarization of radiation-induced Kuptake cells to pro-inflammatory phenotype by inhibiting the CD44 function, so that local inflammatory response, oxidative stress and hepatocyte injury of the liver are relieved. Experiments prove that the CD44 function inhibitor can relieve liver inflammation, improve liver function indexes and reduce liver cell death and tissue pathological damage, and a brand-new and targeted scheme for preventing and treating RILD is provided.

The invention provides application of CAR-NK (chimeric antigen receptor-natural killer) cells in preparation of drugs for treating autoimmune diseases, and the CAR-NK cells express a chimeric antigen receptor and a fusion protein of a targeted NKG2D ligand; the fusion protein comprises an IL-15R alpha and an IL-15, and the IL-15 and the IL-15R alpha are connected with each other. According to the CAR-NK cell disclosed by the invention, the specific recognition of MICA / B molecules on the surface of an over-activated T / B cell of an SLE patient is realized by highly expressing an NKG2D activated receptor, and the durability of an intracellular signal is enhanced so as to resist cell depletion; meanwhile, the super IL-15 fusion protein is expressed to prolong the in-vivo survival and function duration time, and the effect of treating the SLE is improved through the cooperation of the dual mechanisms.

The present disclosure provides a method for chemoselective modification of a cell surface molecule on a target cell. A subject method includes contacting a target cell comprising cell surface molecule comprising a thiol, an amine, or an imidazole with a biomolecule comprising a reactive moiety, wherein the reactive moiety is generated by reaction of a biomolecule (e.g., an antibody) comprising a phenol moiety or a catechol with an enzyme capable of oxidizing the phenol or the catechol moiety. The contacting is carried out under conditions sufficient for conjugation of the cell surface molecule to the biomolecule, thereby producing a modified cell. The present disclosure provides kits for carrying out a subject method. The present disclosure also provides modified cells and methods for using same.

The present disclosure includes a fusion protein or molecule, called a “Macromolecule that depletes PLA2R-specific antibodies”, including a targeting component that specifically binds to a cell surface receptor or other cell surface molecule, and an antigen component fused directly or indirectly to the targeting component. The antigen component is configured to specifically bind target antigen-specific antibodies. The present disclosure also includes a method of depleting target antigen-specific antibodies from a patient by treating the patient with a macromolecule that targets PLA2R-specific antibodies having an antigen component configured to specifically bind the target antigen-specific antibodies.

An object according to certain aspect(s) of the present invention is to provide an immunocompetent cell that expresses regulatory factors of immunocompetent cell immune function and possesses all of proliferative potential, viability, and the ability to accumulate a T cell, and an expression vector of regulatory factors of immune function for generating the immunocompetent cell. An immunocompetent cell expressing a cell surface molecule specifically recognizing a cancer antigen, interleukin 7 (IL-7), and CCL19 is generated. Preferably, the cell surface molecule specifically recognizing a cancer antigen is T cell receptor specifically recognizing the cancer antigen, and the immunocompetent cell is a T cell. Another object according to certain aspect(s) of the present invention is to provide an immunocompetent cell targeting mesothelin. An immunocompetent cell that expresses a cell surface molecule specifically recognizing human mesothelin, interleukin 7 (IL-7), and chemokine (C-C motif) ligand 19 (CCL19) is produced. It is preferred that: the cell surface molecule specifically recognizing human mesothelin should be chimeric antigen receptor (CAR) having single chain antibody, a transmembrane region, and a signaling region that induces the activation of the immunocompetent cell; and the heavy chain variable region and the light chain variable region should be connected via a peptide linker consisting of a 2- to 30-amino acid sequence.

The invention belongs to the field of biomedical examination, and particularly provides a kit for rapidly detecting CD3 molecules of peripheral T cells and a detection method of the kit. The kit comprises a specific anti-CD3 monoclonal antibody, a second antibody, alkaline phosphatase labeled streptavidin, a buffer solution, a color developing agent and a nuclear counterstaining agent. High-sensitivity and high-specificity detection of CD3 molecules is realized through recognition of a specific anti-CD3 monoclonal antibody and cell surface CD3 molecules and application of an enzyme-linked immunosorbent assay technology. The specific detection method comprises the steps of sample treatment, capture reaction, detection reaction, color development and result analysis. The kit disclosed by the invention has the advantages of simplicity and convenience in operation, rapidness in detection, high sensitivity, good specificity and the like, is suitable for laboratory and clinical detection, and provides an efficient and reliable detection tool for immunological research, autoimmune disease diagnosis and tumor immunotherapy effect evaluation.

The invention relates to a therapeutic combination, comprising a first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound to an amino-acid residue of said first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule comprising a second binding site for binding to a second epitope of a second cell-surface molecule different from the first cell-surface molecule, and comprising an effector moiety, wherein the second epitope is different from the first epitope. An aspect of the invention is a composition comprising the first proteinaceous molecule and the second proteinaceous molecule of the invention. The invention also relates to a composition or therapeutic combination comprising an antibody—drug conjugate or antibody—oligonucleotide conjugate and the first proteinaceous molecule of the invention. An aspect of the invention relates to a pharmaceutical composition comprising the composition or the antibody—drug conjugate of the invention, and optionally further comprising a pharmaceutically acceptable excipient. The invention also relates to the therapeutic combination or the composition or the antibody—drug conjugate or the pharmaceutical composition of the invention, for use as a medicament. The invention also relates to the therapeutic combination of the invention for use in the treatment or prophylaxis of a cancer.

Provided herein are anti-adeno-associated virus (AAV) antibodies and antigenic fragments thereof, as well as multispecific antibodies (e.g., bispecific antibodies) that bind to both the capsid of an AAV particle and molecules on a cell surface, related molecular complexes, affinity matrices, and pharmaceutical compositions, and methods for using them. Generally, the present disclosure provides antibodies that bind to the capsid of an adeno-associated virus (AAV) particle, as well as multispecific antibodies, such as bispecific antibodies, that can bind to both the capsid of an AAV particle and molecules on a cell surface (i.e., target molecules), and methods for using them.

Provided are conjugates that can be used for insitu cancer vaccination, such as for cancers with limited accessibility (e.g., lung cancer, pancreatic cancer, renal cancer, etc.) and metastatic disease in situations where the primary tumor has been surgically resected.SOLUTION: Provided are complexes comprising a knottin peptide comprising a modified loop that binds to a cell surface molecule and an immunostimulatory agent conjugated to the knottin peptide via a linker. In some embodiments, the immune stimulating agent activates a pathogen recognition receptor (PRR). For example, the immunostimulatory agent can be a toll-like receptor (TLR) agonist, e.g., an agonist of TLR7, TLR8, and / or TLR9. Also provided are compositions (e.g., pharmaceutical compositions) comprising the complexes of the disclosure, as well as kits comprising such compositions and methods of using such compositions, e.g., to treat an individual having cancer.SELECTED DRAWING: Figure 1

Provided is a cleavable sequence (CS) that can be recognized and cleaved by a protease specifically expressed in the tumor microenvironment. The CS sequence can be recognized and cleaved by a protease specifically expressed in the tumor microenvironment. Further provided is a single-domain antibody capable of neutralizing the activity of an SP34 antibody. Further provided is an isolated polypeptide, which can be a tumor-specifically activated protein drug, and is a prodrug structure having no or extremely low biological activity. The isolated polypeptide comprises 1) a polypeptide (aCD3) that targets and binds to a CD3 molecule on the surface of a T cell; 2) domain 1 (BD1) that blocks the binding of aCD3 to a CD3 molecule on the surface of a T cell; 3) an antibody fragment (aTA) that recognizes and binds to a tumor antigen; and 4) a cleavable linker peptide (CL) that contains a cleavable sequence (CS) and / or 5) domain 2 (BD2) that blocks the binding of aTA to a target antigen thereof.

The present invention relates to a molecule comprising a heterodimer consisting of a first portion comprising a first Fab arm of an antibody and a second portion comprising a second Fab arm of an antibody wherein the first Fab arm and the second Fab arm each comprise an antigen binding domain, the antigen binding domain is for binding to a cell surface molecule on a target cell wherein the first Fab arm comprises at least one moiety capable of being bound by an exogenous immune cell receptor, and wherein the second Fab arm does not comprise any moiety capable of being bound by the exogenous immune cell receptor. Methods for activating immune cells expressing chimeric antigen receptors and for preventing and / or treating various conditions, including cancer, are also contemplated.

This document provides compositions and methods for modulating the internalization properties of cell surface molecules, such as converting non-internalized cell surface antigens into internalized cell surface antigens and converting internalized cell surface antigens into non-internalized cell surface antigens. In some embodiments, engineered antibodies are provided, each comprising an antigen-binding moiety specific to a guide antigen and another antigen-binding moiety specific to an effector antigen, wherein the internalization properties of said engineered antibody or a functional fragment thereof are determined by the relative surface density ratio of said guide antigen to said effector antigen. Recombinant cells, recombinant nucleic acids encoding such engineered antibodies, and pharmaceutical compositions containing them are also provided. This disclosure also provides methods for modulating cell internalization in cells or subjects, and methods for modulating cell type-selective signaling in subjects and / or for treating diseases.

Conjugates comprising an EETI-II based knottin peptide, comprising an engineered loop that binds to a cell surface molecule; and a chelator conjugated to the knottin peptide via a linker may be used for treating cancer in a patient. Conjugates may comprise a radionuclide-chelator complex.

Provided is a novel phase transition adjusting element, a part of which comprises a multivalent phase transition domain, and the remaining comprises at least two ligands, wherein at least one ligand is covalently connected to the part containing the multivalent phase transition structural domain, the remaining ligands are covalently linked to the part comprising the multivalent phase transition structural domain or to other ligands, and each of the at least two ligands can specifically bind to cell surface molecules corresponding thereto. After binding to cell surface molecules, the phase transition adjusting element can effectively enrich cell surface molecules by means of driving phase separation, and enhance the aggregation of cell surface molecules (such as receptor oligomerization), thereby regulating and controlling various cell physiological and biochemical activities, such as receptor downstream signal transmission, cell endocytosis, etc.

The application discloses application of an XYLT1 gene as an antigen presentation regulator in treatment of viral infection. A mouse XYLT1 gene knockout DC2.4 cell line is constructed by using a CRICPR / Cas9 system, and it is found that after the XYLT1 gene is knocked out, the DC2.4-XYLT1 ‑ / ‑ The cell surface MHC I molecule expression is reduced, the role in recognizing and presenting foot-and-mouth disease virus antigens is weakened, the T lymphocyte is prevented from being activated, and the secretion amount of IFN-gamma is reduced. It is indicated that the antigen presentation role of the DC2.4 cell with the XYLT1 gene knocked out is effectively weakened, thereby affecting adaptive immune function of the organism. Therefore, it is of great significance to use the XYLT1 gene as the antigen presentation regulator to regulate adaptive immunity of the organism to the virus, thereby preventing further spread and infection of the virus.

The present disclosure includes a fusion protein or molecule, called a "Macromolecule that depletes ADAMTS13-specific antibodies'; including a targeting component that specifically binds to a cell surface receptor or other cell surface molecule, and an antigen component fused directly or indirectly to the targeting component. The antigen component is configured to specifically bind target antigen-specific antibodies. The present disclosure also includes a method of depleting target antigen-specific antibodies from a patient by treating the patient with a macromolecule that targets ADAMTS13-specific antibodies having an antigen component configured to specifically bind the target antigen-specific antibodies.

Provided are a PD-1 molecule for blocking the binding of an anti-PD-1 antibody to a PD-1 molecule on a cell surface, and a mutant and the use thereof. Further provided is a protein molecule, which has 80-100% sequence identity to a wild-type protein as shown in SEQ ID NO: 1. The provided recombinant protein H126 and H134 molecules can competitively bind to an anti-PD-1 antibody drug with the endogenous PD-1 molecule expressed by a T cell, without affecting the binding of PD-1 to an endogenous PD-L1 molecule, thereby restoring the function suppression on activated T cells and alleviating the symptoms of immunotherapy-related adverse events. By means of the protein molecule, a new way of performing clinical treatment of the immunotherapy-related adverse events is provided.

To provide ADCs and PDCs that enable more effective delivery of cytotoxic drugs to tumor cells.SOLUTION: To provide an endolysosomal targeting conjugate modified to deliver a cargo molecule such as a cytotoxic drug or an imaging label to a late endosome and / or lysosome in a target cell such as a tumor cell with improved efficiency. The endo-lysosomal targeting conjugate comprises a targeting component and a cargo component. The targeting component is configured to bind to a cell surface molecule of a target cell, and the cargo component includes a cargo molecule. The targeting component and the cargo component may be covalently fused or non-covalently associated. The targeting component may bind to a cell surface molecule or cargo component in the extracellular space with higher affinity than in the endolysosomal compartment of the target cell.SELECTED DRAWING: Figure 1

The present application provides a novel phase transition regulating element, which comprises a part containing a multivalent phase transition domain and at least two ligands, wherein at least one ligand is covalently connected to the part containing the multivalent phase transition domain, and the rest of the ligands are covalently connected to the part containing the multivalent phase transition domain or to the other ligands, and each of the at least two ligands can specifically bind to its corresponding cell surface molecule. The phase transition regulating element of the present application can effectively enrich cell surface molecules by driving phase separation after binding to cell surface molecules, enhance the condensation of cell surface molecules (such as receptor oligomerization, etc.), and further regulate a series of cell physiological and biochemical activities, such as receptor downstream signal transmission, cell endocytosis, etc.

The invention provides a multispecific binding protein which can specifically bind to a mannose-6-phosphate receptor (M6PR) and a cell surface molecule or an extracellular molecule, and also provides an antigen binding protein which can specifically bind to CI-M6PR, and applications of the antigen binding protein and the antigen binding protein in mediating lysosome endocytosis degradation, protein transport and disease treatment.

Provided are a group of PD-1 molecules and mutants thereof that block the binding of anti-PD-1 antibodies to cell surface PD-1 molecules and uses thereof. Also provided is a protein molecule that has 80%-100% sequence identity compared to a wild-type protein shown in SEQ ID NO: 1. The provided recombinant protein H126 and H134 molecules can competitively bind to an anti-PD-1 antibody drug expressed by T cell endogenous PD-1 molecules without affecting the binding of PD-1 to endogenous PD-L1 molecules, thereby restoring the functional inhibition of activated T cells and alleviating the symptoms of immune therapy-related adverse reactions. The protein molecules provide a new approach for the clinical treatment of immune therapy-related adverse reactions.