60 results about "Glypican" patented technology

The present disclosure provides amino acid sequences (e.g., antibodies) capable of binding to glypican 3 protein (GPC3). The present disclosure relates to antigen binding fragments of GPC3 antibodies; conjugates of a GPC3 antibody, including an immunoconjugate; bispecific antibodies comprising a GPC3 antibody and related compositions and formulations. The disclosure also relates to methods of treating GPC3-related diseases, disorders and conditions, including cell proliferative diseases, such as cancer, more particularly liver cancer, using these sequences, such as GPC3 antibodies and antigen-binding fragments thereof.

Provided herein are novel Glypican 3 (GPC3) antibodies or antigen binding fragments and GPC3 / CD3 bispecific antibodies. The present application also provides chimeric antigen receptors comprising the antibodies or antigen-binding fragments, related CAR-T cells, and preparation methods and uses of the same. The present application further provides pharmaceutical compositions comprising GPC3 antibodies or antigen binding fragments, related GPC3 / CD3 bispecific antibodies, related GPC3 CAR or CAR-T cells, and methods of treating cancer in a subject in need thereof by administering the Glypican 3 (GPC3) antibodies or antigen binding fragments, the bispecific antibodies, the chimeric antigen receptors, the CAR-T cells, or the pharmaceutical compositions. The cancers treated in accordance with the application include Glypican-3-positive cancers.

Various embodiments of the invention provide binding agents for glypican-3 (GPC3), including antibodies or antigen-binding fragments thereof that bind to GPC3 and antigen recognizing receptors (e.g., CARs) that target GPC3 including cells that express GPC3. Embodiments of the i n vention also provide cells comprising such binding agents such as CAR T-cells, therapeutic compositions comprising such cells and methods of using one or more of the binding agents, cells or therapeutic compositions for the treatment of diseases or disorders associated with GPC3 expression such as various neoplastic diseases or disorders (e.g., hepatocellular carcinoma). Various embodiments of the invention also provide methods and systems for treati ng hepatocellular carcinoma (HCC) utilizing a combi nation of radiofrequency (RF) ablation and GPC3-targeted cell therapy. In certain embodiments, immune modulators, such as checkpoint inhibitors, may be co-administered to potentiate immune responses. Additionally, compositions and kits comprising RF ablation devices and GPC3-targeted cell therapy formulations are provided.

Recombinant antibody T cell receptors (AbTCRs) and chimeric signaling receptors (CSRs) engineered to include antigen-binding domains specific for tumor antigen glypican-2 (GPC2) or glypican-3 (GPC3) are described. Immune cells expressing the AbTCRs and CSRs effectively treated GPC2-positive or GPC3-positive tumors in multiple different xenograft models, and were significantly more potent than similarly targeted chimeric antigen receptor (CAR) T cells.

The gene editing technology was used to carry out target knockout of zc3h12b gene of Oryzias latipes, establishing Oryzias latipes missing Zc3h12b protein product. The established Oryzias latipes all show different degrees of liver lesions such as hepatobiliary duct hyperplasia and fusion, hepatocyte steatosis, and fibrosis. With increase of months, significant fatty liver appears with local cyst necrosis, obvious lymphocyte infiltration in liver sinusoids and abnormal increase in number of macrophages. Human tumor markers cytokeratin 19 (CK19), smooth muscle actin (SMA) and glypican-3 (GPC3) positive cells are also detected. It is suggested that ZC3H12B can be used as a treatment target and a biomarker for biliary cystadenoma (BCA), biliary cystadenocarcinoma (BCAC), or fatty liver or liver cancer related to BCA or BCAC. The zc3h12b missing Oryzias latipes can be used as an animal model in researches on pathological processes of BCA, BCAC, or fatty liver or liver cancer related to BCA or BCAC.

The invention relates to the technical field of radiopharmaceuticals, and discloses a targeted GPC3 polypeptide ligand, which has a structural general formula: C-L-P, wherein C is a chelating group; l is a linker; p is a targeted phosphatidylinositol proteoglycan-3 (GPC3) polypeptide pharmacodynamic group; the linker is a covalent linker or a reversible non-covalent linker. The invention has the following technical effects: by introducing the covalent linker or the reversible non-covalent linker, the chemical structure of the targeted GPC3 polypeptide ligand is optimized, the targeting property of the targeted GPC3 polypeptide radiopharmaceutical is improved, and the pharmacokinetic characteristics are improved; the defects that an existing targeted GPC3 polypeptide radiopharmaceutical is low in tumor uptake, short in tumor residence time, poor in pharmacokinetic characteristic and the like are overcome. The invention further discloses a targeted GPC3 polypeptide radiopharmaceutical as well as a preparation method and application of the targeted GPC3 polypeptide radiopharmaceutical.

The present application provides GPC2-specific antibodies and antigen binding fragments thereof. A chimeric antigen receptor (CAR) that specifically binds glypican-2 (GPC2) comprising a GPC2-specific antibody, a transmembrane domain, and an intracellular signaling domain. T cells comprising the disclosed CAR constructs can be used for cancer immunotherapy.

The present disclosure generally relates to, inter alia, antibodies and chimeric antigen receptors (CARs) that bind a Glypican 2 (GPC2) antigen. The disclosure also provides compositions and methods useful for producing such antibodies and CARs, as well as methods for the diagnosis, prevention, and / or treatment of health conditions associated with the GPC2 antigen expression.

We describe an antibody or antigen binding fragment thereof comprising a cloned heavy chain variable region (VH) sequence and a light chain variable region (VL) sequence selected from the group consisting of 5C4, 4H1, 1D2, 1C4, 2B5, 1F1, 1H1, 4A5, 1D8, 1D3, 2F1, 3C6, 3D12, 3A9, 1F4, 1H10, 3C12, 4G11, 4A12, 1A12, 3G12, 4F9, 4G4 and 1E1, said antibody or antigen binding fragment thereof being capable of binding specifically to glypican-3 (GPC-3) (Genbank accession number: NP004475.1), or a sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity thereto.

The present technology generally relates to peptides that bind to phosphatidylinositol proteoglycan 3 (GPC3), to peptides that bind to the GPC3, and to compositions comprising such peptides.

The invention relates to compositions comprising D-xylose-2-phosphate, the esters thereof, and / or oligosaccharides comprising D-xylose-2-phosphate. These compositions can be used as medicaments, in particular in the prevention or treatment of infection with viruses, using syndecans and / or glypicans as cell receptors. These compositions can also be used in cosmetics or as food supplements.

The present technology relates to the field of cancer treatment. In particular, the present technology relates to polypeptides targeting phosphatidylinositolprotein-3 (GPC3) and T cell receptor (TCR) for use in the treatment of phosphatidylinositolprotein-3 positive (GPC3 +) solid tumors, such as hepatocellular carcinoma (HCC) or non-small cell lung cancer (NSCLC). In addition, the technology relates to the dosage of said polypeptide when used as therapy.

Monoclonal antibodies that bind glypican-2 (GPC2) with high affinity are described. Immunotoxins and chimeric antigen receptors (CARs) that include the disclosed antibodies or antigen-binding fragments thereof are further described. In some instances, the antibody or antigen-binding fragment is humanized. The disclosed GPC2-specific antibodies and conjugates can be used, for example, for the diagnosis or treatment of GPC2-positive cancers, including neuroblastoma, medulloblastoma and retinoblastoma.

We describe an antibody or antigen-binding fragment thereof comprising a heavy chain variable region (VH) sequence and a light chain variable region (VL) sequence of a clone selected from: 5C4, 4H1, 1D2, 1C4, 2B5, 1F1, 1H1, 4A5, 1D8, 1D3, 2F1, 3C6, 3D12, 3A9, 1F4, 1H10, 3C12, 4G11, 4A12, 1A12, 3G12, 4F9, 4G4 and 1E1 which is capable of specifically binding to glypican-3 (GPC-3) (GenBank Accession Number: NP_004475.1), or a sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity thereto.

Nucleic acid constructs encoding chimeric antigen receptors (CARs) and truncated human epidermal growth factor receptors (huEGFRt) are described. The encoded CARs include tumor antigen-specific monoclonal antibodies fused to CD8α hinge regions, CD8α transmembrane regions, 4-1BB costimulatory domains, and CD3ζ signaling domains, such as glypican-3 (GPC3)-specific, GPC2-specific, or mesothelin-specific monoclonal antibodies. Separated host cells are also described, such as separated T cells co-expressing the disclosed CARs and huEGFRt. T cells transduced with the disclosed CAR constructs can be used for cancer immunotherapy.

Optimized chimeric antigen receptors (CARs) targeting glypican-2 (GPC2) and having a CD28 hinge region and a CD28 transmembrane domain are described. The antigen-binding domain of the disclosed CARs is derived from GPC2-specific antibody CT3 or humanized versions thereof. The optimized CARs also include an intracellular co-stimulatory domain and an intracellular signaling domain. Immune cells or induced pluripotent stem cells expressing the optimized CARs can be used to treat GPC2-positive solid tumors, such as neuroblastoma.

We describe an antibody or antigen-binding fragment thereof comprising a heavy chain variable region (VH) sequence and a light chain variable region (VL) sequence of a clone selected from: 5C4, 4H1, 1D2, 1C4, 2B5, 1F1, 1H1, 4A5, 1D8, 1D3, 2F1, 3C6, 3D12, 3A9, 1F4, 1H10, 3C12, 4G11, 4A12, 1A12, 3G12, 4F9, 4G4 and 1E1 which is capable of specifically binding to glypican-3 (GPC-3) (GenBank Accession Number: NP_004475.1), or a sequence having at least 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity thereto.

The present invention relates to a chimeric antigen receptor comprising a phosphatidylinositol proteoglycan 2 binding domain. The present disclosure relates to chimeric antigen receptors that bind to phosphatidylinositol proteoglycan 2, nucleic acids encoding the same, and cells that express the same, and methods of using such cells to treat cancers that express or overexpress a phosphatidylinositol proteoglycan 2 antigen.

The present invention provides a plurality of monoclonal antibodies capable of recognizing glypican 3 (GPC3) with high affinity. The monoclonal antibodies not only have high affinity, but also cover a plurality of epitopes of GPC3, and can be used for detecting a tumor marker GPC3 by a sandwich method. The monoclonal antibody provided by the invention not only has good thermal stability, but also has excellent cytotoxic activity after being conjugated with pseudomonas exotoxin PE24, is obviously superior to the existing immunotoxin HN3-PE24, and can be used for developing immunotoxin or antibody-drug conjugate (ADC) drugs with stronger activity and better stability.

A single-domain monoclonal antibody with high affinity for the tumor antigen glypican-3 (GPC3), which was functionalized with a chelating group and radiolabeled with a positron-emitting radionuclide (18F), is described. The radiolabeled GPC3-specific single-domain antibody exhibited an exceptionally high tumor to liver binding ratio, enabling its use to accurately detect GPC3-positive liver tumors, such as hepatocellular carcinoma (HCC). The radiolabeled GPC3-specific single-domain antibody can be used, for example, as an imaging agent in positron-emission tomography (PET)-based detection of GPC3-positive tumors.

The invention relates to compositions comprising D-xylose-2-phosphate, its esters, and / or oligosaccharides comprising D-xylose-2-phosphate. These compositions can be used as a medicinal product, particularly in the prevention or treatment of viral infections using syndecanes and / or glypicans as cell receptors. These compositions can also be used in cosmetics or as a food supplement.

This disclosure relates to anti-GPC1 (Glypican-1) antibodies, antigen-binding fragments thereof, and the uses thereof including also in the form of antibody-drug conjugates intended for cancer therapies.

The present disclosure provides antibodies specific for glypican-3 (GPC3). Nucleic acids that encode one or both of the variable chain polypeptides of an antibody of the present disclosure are also provided, as are cells that include such nucleic acids. Also provided are compositions that include the antibodies of the present disclosure, including in some instances, pharmaceutical compositions. Methods of making and using the antibodies of the present disclosure are also provided. In certain aspects, provided are methods that include administering to an individual having a cell proliferative disorder a therapeutically effective amount of an antibody of the present disclosure, where the antibody is administered to the individual to enhance an immune response, e.g., a T cell response, to abnormally proliferating cells of the cell proliferative disorder. The antibodies are useful in various diagnostic, and monitoring applications, which are also provided.

The present invention relates to a fully humanized single-domain antibody against Glypican-3 and its application; the antibody comprises 3 heavy-chain complementarity-determining regions (CDRs), wherein the amino acid sequence of CDR1 is the amino acid sequence at positions 31-35 of SEQ ID NO:1; the amino acid sequence of CDR2 is the amino acid sequence at positions 50-66 of SEQ ID NO:1; and the amino acid sequence of CDR3 is the amino acid sequence at positions 99-107 of SEQ ID NO:1. The present invention utilizes phage display technology to screen for antibodies by targeting human GPC3 protein, and obtains 1 specific fully human monoclonal single-domain antibody against human GPC3; the antibody can specifically bind to human GPC3 and can effectively inhibit the activation of Wnt signal, providing an effective alternative antibody drug for the treatment of HCC targeting GPC3, and having potential clinical application prospects.

The invention relates to the technical field of medicines, in particular to a bionic nano adjuvant and application thereof. The preparation method comprises the following steps: taking selenium element modified mesoporous nano silicon dioxide as a carrier, loading fatty acid synthase small interfering RNA (FASN siRNA) and an antiviral drug entecavir (ETV) on the carrier to obtain a carrier loaded with a drug, then coating the carrier loaded with the drug by using a liver cancer cell membrane to obtain a cell membrane-carrier, and preparing the liver cancer cell membrane-carrier. And finally, coupling a phosphatidylinositol proteoglycan 3 (GPC3) antibody with the cell membrane of the cell membrane-carrier to obtain the bionic nano adjuvant. The bionic nano adjuvant provided by the invention has targeting property and relatively good biocompatibility, can deliver anti-tumor drugs into hepatocytes in a targeting manner, can also reduce active oxygen and lipid levels in a tumor microenvironment, and has application value in the fields of treatment of chronic hepatitis B and the like.

This application relates to the field of tumor immunodiagnostic technology, and particularly to a monoclonal antibody, polynucleotide, preparation method, and application of antiphosphatidylinositol proteoglycan-3; the monoclonal antibody includes a heavy chain variable region and a light chain variable region, wherein the heavy chain variable region includes heavy chain region CDR1 with amino acid sequence as shown in SEQ ID NO:1, heavy chain region CDR2 with amino acid sequence as shown in SEQ ID NO:2, and heavy chain region CDR3 with amino acid sequence as shown in SEQ ID NO:3; the light chain variable region includes light chain region CDR1 with amino acid sequence as shown in SEQ ID NO:4, light chain region CDR2 with amino acid sequence as shown in SEQ ID NO:5, and light chain region CDR3 with amino acid sequence as shown in SEQ ID NO:6; the dissociation constant KD(M) of the monoclonal antibody against GPC3 antigen is 1.21E-11, which is a high-affinity N-terminal antibody, suitable for the detection of GPC3 in clinical serum samples.

This disclosure relates to anti-GPC1 (Glypican-1) antibodies, antigen-binding fragments thereof, and the uses thereof including also in the form of antibody-drug conjugates intended for cancer therapies.

Provided herein are polypeptides which include tenth fibronectin type III domains (10Fn3) that bind to glypican-3. Also provided are fusion molecules comprising a 10Fn3 domain that bind to glypican-3 for use in diagnostic and therapeutic applications. Glypican-3 10Fn3 drug conjugates are also provided.

The present invention provides radiopharmaceuticals and conjugates targeting GPC3 as well as compositions and uses thereof. In one aspect, provided herein are conjugates comprising a peptide having affinity for GPC3 and a metal chelating agent configured to bind to a radionuclide. The conjugates described herein may further comprise a linker linking the chelating agent and the peptide. The conjugates described herein may further comprise radionuclides. In one aspect, provided herein is a radiopharmaceutical comprising a peptide and a metal chelating agent that binds to a radionuclide. The conjugates described herein may further comprise a linker linking the chelating agent and the peptide. Further provided herein are methods of treating cancer by administering the described radiopharmaceuticals, conjugates, compositions thereof.

SCGB-based preparations and methods to use these preparations to protect the glycocalyx in medical, veterinary, and cosmetic applications are provided. The secretoglobins (SCGBs) are a family of small secreted globular proteins present in all mammals and sharing conserved structure and thought to share similar immunomodulatory functions. Heparan sulfate proteoglycan proteins (HSPGs) are expressed on the outer membranes of cells and have carbohydrate side chains that, together, make up the glycocalyx. The glycocalyx is a protective layer surrounding all cells, acting as a filter regulating the passage of nutrients into the cell and modifying cell signaling by external factors. There are two major families of HSPGs including syndecans and glypicans, plus several other HSPGs in all mammals. SCGBs bind to, and interact with, HSPGs to further modulate cell signaling and cellular responses to external factors.