81 results about "Cell surface molecules" patented technology

Compositions and methods for treating diseases associated with aberrant glycosylation of cell surface molecules and expression of tumor-associated carbohydrate antigens (TACAs) are provided. Also provided are fusion proteins having specificity for tumor-associated carbohydrate antigen (TACA) comprising a half-life extender molecule, vectors encoding the TACA-fusion proteins, and recombinant cells comprising the TACA-specific fusion proteins.

Compositions and methods for treating diseases associated with aberrant glycosylation of cell surface molecules and expression of tumor-associated carbohydrate antigens (TACAs) are provided. Also provided are bispecific fusion proteins and chimeric antigen receptors (CARs) having specificity for tumor associated carbohydrate antigen (TACA-CAR), vectors encoding the TACA-bispecific fusion proteins and CARs, and recombinant cells comprising the TACA-bispecific fusion proteins and CARs.

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 an antibody-drug conjugate comprising the first proteinaceous molecule of the invention and an effector moiety. 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.

The application relates to a T cell-targeting nanoparticle based on a nucleic acid aptamer and a preparation method and application thereof, in particular to a T cell-targeting lipid aptamer, wherein the lipid aptamer comprises a hydrophobic molecule and a nucleic acid aptamer, the nucleic acid aptamer comprises at least one nucleic acid aptamer for targeting a T cell surface molecule, and the molar ratio of the hydrophobic molecule and the nucleic acid aptamer is 5000:1-1:10. The lipid aptamer or the nanoparticle formed by self-assembly technology of the lipid aptamer can realize cell 'pointing' gene modification and in-vivo gene reprogramming of cells.

The application discloses a method for separating rat intestinal nerve cells, takes the intestinal muscle layer of a rat intestine and digests it into single cells, and then purifies the rat intestinal nerve cells by performing flow antibody staining and flow cytometry sorting on cell surface molecules such as CD9 and CD45, and comprises the following general steps: firstly, single cell preparation, secondly, single cell staining, and finally, flow cytometry separation. The application has a short time consumption and can realize real-time separation; the cell surface molecule markers for the rat intestinal nerve cells are determined to be CD45 negative and CD9 positive, and the rat intestinal nerve cells can be rapidly separated in real time for scientific research and clinical use.

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.

Disclosed herein are monospecific and bispecific antibodies that comprise a ALPPL2 / ALPP-binding variable region. The bi-specific antibody is comprises of a monoclonal antibody targeting a tumor-specific cell surface antigen (ALPPL2 / ALPP) with exquisite tissue specificity and a monoclonal antibody targeting a cell surface molecule (e.g., CD3) expressed by immune effector cells.

Dysfunctional or exhausted T cells arise in chronic diseases including chronic viral infections and cancer, and express high levels of co-inhibitory receptors. Therapeutic blockade of these receptors has clinical efficacy in the treatment of cancer. While co-inhibitory receptors are co-expressed, the triggers that induce them and the transcriptional regulators that drive their co-expression have not been identified. The immunoregulatory cytokine IL-27 induces a gene module in T cells that includes several known co-inhibitory receptors (Tim-3, Lag-3, and TIGIT). The present invention provides a novel immunoregulatory network as well as novel cell surface molecules that have an inhibitory function in the tumor microenvironment. The present invention further provides the novel discovery that the transcription factors Prdm1 and c-Maf cooperatively regulate the expression of the co-inhibitory receptor module. This critical molecular circuit underlies the co-expression of co-inhibitory receptors in dysfunctional T cells and identifies novel regulators of T cell dysfunction.

The invention discloses application of mycobacterium protein in preparation of an antigen presentation inhibitor. The amino acid sequence of the mycobacterium protein is as shown in SEQ ID NO: 1, and the protein does not generate excessive immunological rejection; secondly, the protein can inhibit the expression of surface molecules of antigen presenting cells and inhibit the occurrence of acquired immune response; the protein inhibits host antigen presentation through multiple factors and multiple ways, and inhibits acquired immunity.

The present invention relates to a bifunctional molecule formed by fusion of a PD1 antibody and interleukin 2, comprising: a heterodimer composed of a first monomer and a second monomer as follows: (1) a first monomer, formed by linking interleukin 2 (IL2) to an immunoglobulin Fc single chain; and (2) a second monomer, formed by linking an Fab / ScFv of an anti-T cell surface molecule antibody to an Fc single chain. The bifunctional molecule may also be a homodimer comprising a monomer comprising: (1) an interleukin 2 functional block; and (2) a monomer of an antibody or a monomer formed by linking an Fab / ScFv of an antibody to an Fc single chain, the antibody being an anti-T cell surface molecule antibody. The present invention further relates to use of the bifunctional molecule in the manufacture of anti-tumor medicament.

The invention relates to a conjugate for transferring an effector molecule from outside a cell into said cell, the conjugate comprising at least one effector molecule to be transferred into the cell, at least one saponin of the mono-desmosidic triterpene glycoside type or the bi-desmosidic triterpene glycoside type, and at least one single-domain antibody (sdAb), covalently bound to each other, wherein the sdAb is capable of binding to a cell-surface molecule of said cell. The invention also relates to a pharmaceutical composition comprising the conjugate of the invention. Furthermore, the invention relates to a pharmaceutical composition of the invention, for use as a medicament. In addition, the invention relates to a pharmaceutical composition of the invention, for use in the treatment or the prophylaxis of any one or more of: a cancer, an auto-immune disease such as rheumatoid arthritis, an enzyme deficiency, a disease related to an enzyme deficiency, a gene defect, a disease relating to a gene defect, an infection such as a viral infection, hypercholesterolemia, primary hyperoxaluria, haemophilia A, haemophilia B, alpha-1 antitrypsin related liver disease, acute hepatic porphyria, an amyloidosis and transthyretin-mediated amyloidosis. The invention also relates to an in vitro or ex vivo method for transferring the conjugate from outside a cell to inside said cell or for transferring the effector molecule comprised by the conjugate of the invention from outside a cell to inside said cell, preferably to the cytosol of said cell.

A method for measuring kinetics of Ca2+ flux in differentially responding T cells that form monolayer on the glass surface in response to antigenic peptides or live target cells comprising: immobilizing T cells labeled with Ca2+ sensitive fluorophore on the glass bottom of a well, covered with capturing antibody or a capturing protein that bind to non-stimulatory T-cell surface receptor; adding to the well a single or multiple peptide epitopes that binds to the cell surface MHC molecules to be presented for recognition by cognate T cells; the stimulatory signal could also be delivered by live target cells that display peptide epitope(s); wherein the recognition of stimulatory of pMHC by the peptide specific T cells leads to increase of intracellular Ca2+ level and fluorescence intensity in the responding T cells, which is then identified after the subtracting fluorescence intensity for every T cell before and after the addition of the peptide antigens; scoring each responding T cell into a category according to three categories including: a rapid and sustained T-cell response, an oscillatory response, or a delayed and oscillatory response; and measuring changes in number of an individual T cells with increased intracellular fluorescence as function of time provides the kinetic curve of the TCR-mediated Ca2+ signaling.

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 present application relates to a kind of molecular marker group of human esophageal squamous cell carcinoma and its application, the molecular marker group is: the molecular marker group that the esophageal squamous cell carcinoma is divided into differentiation type, immune type, metabolic type, cell stem type: differentiation type: LCE3D, CDSN, KLK5, SPRR2G and DSG1;Immune type: MS4A1, CD79A, CXCL9, MZB1 and IDO1;Metabolic type: GSTA1, ADH7, UGT1A3 and ALDH3A1;Cell stem type: WFDC2, PEG10, SFRP1, LGR6 and VWA2;And the NK cell surface molecular marker group that the esophageal squamous cell carcinoma is divided into prognosis bad and drug insensitivity subtype.

The invention relates to a system for detecting a cell surface PTK7 molecular diffusion coefficient based on a single molecule tracing technology and application thereof, and belongs to the technical field of cancer cell detection. The system comprises a single-molecule tracing fluorescence labeling probe, a single-molecule total internal reflection fluorescence microscope, an image acquisition module and an image processing module. The single-molecule tracing fluorescence labeling probe comprises a labeling unit targeting PTK7 and a single-molecule tracing fluorescence group. The probe has small interference on the structure and movement of PTK7 protein molecules, can realize excellent in-situ, interference-free, real-time and dynamic tracking of the movement of PTK7 protein in various tumor cells, and accurately displays the movement track of the target protein. The system can track and detect motion data of PTK7 proteins of normal cells and tumor cells, and further performs statistics, arrangement and analysis to obtain a dynamic motion rule of PTK7 molecules. The rule can be used as a novel biophysical index for evaluating the invasion and metastasis potential of tumor cells, and is used for early diagnosis and targeted therapy of tumor metastasis.

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 invention relates to a therapeutic combination comprising a first protein molecule comprising a first binding site for binding a first epitope of a first cell surface molecule and comprising a second pharmaceutical composition, the first pharmaceutical composition comprises a first protein molecule having at least one saponin covalently bound to an amino acid residue of the first protein molecule, and a second pharmaceutical composition comprising a second protein molecule different from the first protein molecule, the second protein molecule comprises a second binding site for binding a second epitope of a second cell surface molecule different from the first cell surface molecule, and comprises an effector moiety wherein the second epitope is different from the first epitope. Aspects of the invention are compositions comprising the first protein molecule and the second protein molecule of the invention. The invention also relates to antibody-drug conjugates comprising said first protein molecule of the invention and an effector moiety. Aspects of the invention relate to pharmaceutical compositions comprising said composition or said 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 said therapeutic combination of the invention for use in the treatment or prevention of cancer.

To provide a conjugate for transferring an effector molecule from outside a cell into said cell.SOLUTION: Provided is a conjugate comprising an effector molecule, a cell surface molecule targeting antibody, and a saponin. Therein: the effector molecule, the antibody, and the saponin are covalently bound to each other; the effector molecule is an oligonucleotide; the saponin is a bi-desmosidic triterpene glycoside comprising an aglycone core structure selected from quillaic acid or gypsogenin and comprising a first glycan bound to a C3 atom of the aglycone core structure and a second glycan bound to a C28 atom of the aglycone core structure; the first glycan is branched and comprising a glucuronic acid unit; the second glycan is branched and comprising a carbohydrate unit selected from any one or more of fucose (Fuc), rhamnose (Rha), and quinovose (Qui); and the antibody is capable of binding to a cell surface molecule of the cell.SELECTED DRAWING: None

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 invention relates to multi-specific T cell engagers and the use thereof. Specifically, the present invention provides the multi-specific T cell engager, comprising a first targeting domain targeting leucine-rich repeat containing protein 15 (LRRC15) molecules highly expressed on the surface of a tumor cell, and further comprising a second targeting domain and / or a third targeting domain bound to the CD molecules of T cell surface. The LRRC15 related multi-specific T cell engagers of the present invention can effectively activate T cells and reduce the tumor stroma impact, and can be used as an effective therapeutic agent for treatment of tumors, especially tumors with a high expression level of LRRC15.

The present application provides methods and systems for improved production of cells (e.g., engineered immune cells) that are readily self-killer. In some cases, the production of engineered immune cells that are readily self-killer expressing chimeric antigen receptor (CAR) molecules that are capable of binding cell surface molecules expressed by other immune cells that likewise express the same CAR molecule may limit the viability and yield of the engineered immune cells. As described herein, methods and systems that allow for control of parameters such as metabolite concentration and cell mass formation during culture may in some cases be used to increase yield and / or viability in the production of cells that are susceptible to self-killer. Also provided herein is an engineered immune cell, a population of engineered immune cells, and / or a pharmaceutical composition comprising an engineered immune cell or a population of engineered immune cells produced using the methods or systems described herein.

To provide an improved biologically active compound useful in the treatment or prevention of cancer, or a composition comprising the compound.SOLUTION: The invention relates to a therapeutic combination comprising a first proteinaceous molecule including a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule being provided with at least one saponin covalently bound to an amino acid residue of the first proteinaceous molecule, and comprising a second pharmaceutical composition comprising a second proteinaceous molecule different from the first proteinaceous molecule, the second proteinaceous molecule including 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. A composition comprising the first proteinaceous molecule and the second proteinaceous molecule, an antibody-drug conjugate comprising the first proteinaceous molecule and an effector moiety, and the like are provided.SELECTED DRAWING: None

The present disclosure describes lysosome-targeting chimeras having at least one target-binding moiety capable of specifically binding a cell surface molecule or an extracellular molecule; and at least one thiol-responsive moiety. Methods of making and using the lysosome-targeting chimeras are also provided.

The invention discloses an application of Rv1039c protein in preparation of an antigen presentation inhibitor, the amino acid sequence of the protein is as shown in SEQ ID NO: 1, and the protein does not generate excessive immunological rejection; secondly, the protein can inhibit the expression of surface molecules of antigen presenting cells and the occurrence of adaptive immune response; the protein inhibits host antigen presentation through multiple ways and inhibits adaptive immunity.

The present application relates to immunocompetent cells and expression vectors expressing immune function regulatory factors. The subject of the present invention is to provide immunocompetent cells expressing immune function regulatory factors of immunocompetent cells and having both proliferation ability, survival ability, and T cell aggregation ability, and to provide immunocompetent cells for preparing the immune function regulatory factor expression vectors of the immunocompetent cells. Prepare immunocompetent cells expressing cell surface molecules that specifically recognize cancer antigens, interleukin 7 (IL-7), and CCL19. The cell surface molecules that specifically recognize cancer antigens are preferably T cell receptors that specifically recognize cancer antigens, and the immunocompetent cells are preferably T cells.

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.