43 results about "Glypican" patented technology

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 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.

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.

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.

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.

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.

Embodiments of the present disclosure provide an antibody comprising a light chain variable domain and a heavy chain variable domain. The light chain variable domain comprises a CDRL1 with an amino acid sequence as set forth in SEQ ID NO:8; a CDRL2 with an amino acid sequence as set forth in SEQ ID NO:10; and a CDRL3 with an amino acid sequence as set forth in SEQ ID NO:12. The heavy cham variable domain comprises a CDRH1 with an amino acid sequence as set forth in SEQ ID NO:4; a CDRH2 with an amino acid sequence as set forth in SEQ ID NO:16; and a CDRH3 with an amino acid sequence as set forth in SEQ ID NO:18; wherein the antibody specifically binds glypican-3 (GPC3).

This technology aims to provide a novel type of drug for treating patients suffering from cancer. [Solution] Specifically, this technology provides a polypeptide comprising at least four immunoglobulin monovariable domains (ISVDs), characterized in that one ISVD binds to the TCR and at least two ISVDs bind to GPC3. This technology also provides nucleic acids, vectors, and compositions.

The present disclosure relates to the discovery of compositions and methods for therapeutic immunization for SARS-CoV-2 infections and / or disease(s) associated with expression of Glypican-3 (GPC3), including but not limited to cancers such as hepatocellular carcinoma (HCC). Methods of the disclosure include a method of generating virus like vesicles (VLVs), VLVs comprising SARS-CoV-2 antigens from a high titer VLV producing vector, VLVs comprising GPC3 antigens from a high titer VLV producing vector, methods of treating, ameliorating, and / or preventing SARS-COV-2 infection, methods of inducing a memory T and B cell immune response against SARS-CoV-2 infection in a, methods of treating, ameliorating, and / or preventing GPC3 associated disease, and methods of inducing a memory T and B cell immune response against GPC3 in a subject. Furthermore, the disclosure encompasses a pharmaceutical composition for vaccinating a subject to protect the subject against infection with

Nucleic acid constructs encoding a chimeric antigen receptor (CAR) and a truncated human epidermal growth factor receptor (huEGFRt) are described. The encoded CAR includes a tumor antigen specific monoclonal antibody, such as a glypican-3 (GPC3)-specific, GPC2-specific or mesothelin-specific monoclonal antibody, fused to a CD8 [alpha] hinge region, a CD8 [alpha] transmembrane region, a 4-1BB co-stimulatory domain, and a CD3 [zeta] signaling domain. Also described are isolated host cells, such as isolated T cells that co-express the disclosed CAR and huEGFRt. The T cells transduced with the disclosed CAR constructs can be used in cancer immunotherapy.

The disclosure relates to multimers of Glypican-3 (GPC3)-, CD44-, and Epithelial cell adhesion molecule (EpCAM)-specific peptides and the use thereof to detect and treat epithelial cell-derived cancers such as hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), breast cancer, colon cancer, gastric cancer, ovarian cancer, cervical cancer, and basal cell carcinoma of the skin. The disclosure also relates to methods to monitor the therapeutic response of treated patients using the peptide multimers.

The invention discloses a pharmaceutical composition for treating cancers and application thereof. The pharmaceutical composition comprises natural killer cells activated by in vitro amplification and a bispecific antibody specifically targeting to Glypican-3 and CD16A. The invention provides a specific amino acid sequence of the bispecific antibody and a high-purity sorting and large-scale amplification method of natural killer cells. In-vitro experiments prove that the composition has remarkable specific killing activity on Glypican-3 high-expression liver cancer cells and can effectively activate natural killer cells to secrete IFN-gamma and TNF-alpha. Animal in-vivo experiments further prove that the composition can effectively inhibit tumor growth, and meanwhile, the lifetime of tumor-bearing mice is remarkably prolonged. The invention provides a brand new and efficient immunotherapy strategy for Glypican-3 positive malignant tumors.

Described herein are antibody-drug conjugates (ADCs) comprising an antibody construct that binds to human glypican 3 (GPC3) conjugated to a camptothecin analog of formula (I). The ADCs are useful as therapeutic agents, particularly in the treatment of cancer.

Provided are a glypican-3 (GPC3)-specific modified aptamer, and prevention or treatment of hepatoma using the same. The glypican-3-specific modified aptamer of the present invention specifically binds to glypican-3 to be internalized into hepatoma cells, and exhibits anticancer activity through an anticancer agent bound to the aptamer, and therefore, has a selective anticancer effect only for GPC3-expressing hepatoma cells without affecting normal hepatocytes.

The present invention relates to a glypican 3 single-domain antibody and its application. The amino acid sequence of CDR1 of the single-domain antibody includes the sequence shown in SEQ ID NO.1, the amino acid sequence of CDR2 includes the sequence shown in SEQ ID NO.2, and the amino acid sequence of CDR3 includes the sequence shown in SEQ ID NO.3. The present invention utilizes eukaryotically expressed GPC3 fusion protein to immunize camels, construct a phage display library, and screen to obtain glypican 3 single-domain antibodies with good specificity and affinity. At the same time, they have the characteristics of low molecular weight, which can effectively develop therapeutic drugs, engineered immune cells, and detection reagents.