73 results about "Glypican 3" patented technology

An antibody capable of binding to a specific region of glypican 3, as well as a humanized antibody created based on that antibody are disclosed. The anti-GPC3 antibody of the invention has a higher ADCC activity and CDC activity compared with those of a conventional antibody. The antibody of the present invention is useful as a cell growth inhibitor, an anticancer agent and an agent for diagnosis of cancers.

A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.

The invention relates to a chimeric antigen receptor of a targeted GPC3 (Glypican 3) and an application thereof. Specifically, the invention provides a polynucleotide sequence, wherein the polynucleotide sequence is selected from: polynucleotide sequences (1) containing a coding sequence of a CD8 antigen leading peptide, a coding sequence of an anti-GPC3 single-chain antibody, a coding sequence of a human CD8 alpha hinge region, a coding sequence of a human CD8 transmembrane region, a coding sequence of a human 41BB intracellular region, and a coding sequence of a human CD3 zeta intracellular region, and a coding sequence of an optional fragment of an EGFR (Epidermal Growth Factor Receptor) sequence containing an extracellular domain III and an extracellular domain IV, wherein the coding sequences are sequentially connected; and complementary sequences (2) of the polynucleotide sequences (1). The invention provides a CAR (chimeric antigen receptor) coded by the polynucleotide sequences and a T cell expressing the CAR. The prepared CAR-T cell has a function of strongly killing a specific tumor cell, and the kill effectiveness is more than 90% under the condition that the effector-target ratio is 20:1.

A method is provided for screening a subject for hepatocellular carcinoma by determining the level of glypican-3 (GPC3) in a body fluid sample from the subject. A further method is provided for diagnosing hepatocellular carcinoma by detecting GPC3 in a liver tissue sample. Also provided are antibodies which bind specifically to GPC3.

Disclosed is an antibody against a secreted form of GPC3 capable of detecting a secreted form of glypican 3 (GPC3) in a test sample. It is possible to determine whether a subject suffers from cancer, in particular hepatoma. Also disclosed is an antibody against GPC as well as a cell disrupting agent and an anti-cancer agent comprising the same, which can disrupt cells, in particular cancer cells.

An anti-glypican 3 antibody with modified sugar chains, more specifically, an anti-glypican 3 antibody lacking fucose is provided. The anti-glypican 3 antibody with modified sugar chains of the present invention may be produced by a process comprising introducing a nucleic acid encoding an anti-glypican 3 antibody into host cells with reduced fucose addition capability, such as YB2 / 0 cells and cells lacking a fucose transporter. The anti-glypican 3 antibody with modified sugar chains of the present invention has a high level of cytotoxic activity and therefore is useful as a cell growth inhibitor such as an anticancer agent.

Provided is a method for diagnosing cancer by detecting a novel cancer marker. Cancer can be diagnosed by detecting soluble glypican 3 in a test sample.

A method of modulating the plasma half-life of anti-glypican 3 antibody, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody that has a plasma half-life that has been modulated, a method of preparing the anti-glypican 3 antibody and a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient are provided. Disclosed is a method of modulating the plasma half-life of anti-glypican 3 antibody by modifying an amino acid residue that is exposed on the surface of the anti-glypican 3 antibody; and anti-glypican 3 antibody that has a plasma half-life that has been modulated by amino acid residue modification, a pharmaceutical composition comprising as an active ingredient the anti-glypican 3 antibody, and a method of preparing the anti-glypican 3 antibody and producing a pharmaceutical composition comprising the anti-glypican 3 antibody as an active ingredient.

An anti-glypican 3 antibody with modified sugar chains, more specifically, an anti-glypican 3 antibody lacking fucose is provided. The anti-glypican 3 antibody with modified sugar chains of the present invention may be produced by a process comprising introducing a nucleic acid encoding an anti-glypican 3 antibody into host cells with reduced fucose addition capability, such as YB2 / 0 cells and cells lacking a fucose transporter. The anti-glypican 3 antibody with modified sugar chains of the present invention has a high level of cytotoxic activity and therefore is useful as a cell growth inhibitor such as an anticancer agent.

Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and / or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.

The present invention provides an anti-cancer agent comprising anti-glypican 3 antibody wherein the anti-cancer agent is administered after a cancer treatment, Preferably, after a cancer treatment is after a treatment for liver cancer, and the treatment for liver cancer is in particular a resection of liver cancer cells. The anti-cancer agent according to the present invention is preferably administered if glypican 3 is expressed in the resected liver cancer cells. The anti-glypican 3 antibody is preferably a monoclonal antibody. The anti-cancer agent according to the present invention is useful for preventing cancer and for preventing the recurrence of cancer.

Provided is a cell growth inhibitor that can be used for treating diseases based on abnormal cell proliferation, and in particular cancer. The cell growth inhibitor contains an anti-glypican 3 antibody as an active ingredient.

Provided are a pharmaceutical composition for prevention and treatment of a neural disease including at least one selected from the group consisting of mesenchymal stem cells (MSCs), a culture solution of the MSCs, activin A, PF4, decorin, galectin 3, GDF15, glypican 3, MFRP, ICAM5, IGFBP7, PDGF-AA, SPARCL1, thrombospondin-1, WISP1, progranulin, IL-4, a factor inducing expression thereof, and any combination thereof, and a method therefor.

Disclosed is a cholangiocarcinoma cell growth inhibitor comprising an anti-glypican-3 antibody as an active ingredient. Preferably, the anti-glypican-3 antibody has a cytotoxic activity such as an antibody-dependent cytotoxic (ADCC) activity and a complement-dependent cytotoxic (CDC) activity. Also disclosed is a diagnostic agent for diagnosis of cholangiocarcinoma comprising an anti-glypican-3 antibody.

The invention discloses a nanobody of the anti-GPC 3 (Glypican 3) protein and a preparation method and application of the nanobody. A prokaryotic expression GPC 3 fusion protein is used to immunize acamel, the RNA in a spleen tissue of the camel is extracted and is used as a template to implement inverse transcription to form cDNA, the cDNA is constructed to a carrier of an outer capsid protein of a bacteriophage to construct a bacteriophage display library, and the storage capacity and the titer are calculated. Then the nanobody specifically combined with the GPC 3 is screened from the library according to the antigen-antibody affinity principle after elutriating for three times, a gene of the specific antibody is then obtained, an expression carrier is constructed, the prokaryotic expression is implemented, the expression carrier is purified and identified, and the required nanobody is obtained.

The invention relates to the field of tumor cellular immunotherapy, and in particular relates to a recombinant lentivirus and application thereof. The recombinant lentivirus comprises a chimeric antigen receptor, wherein the chimeric antigen receptor mainly comprises signal peptide, an antigen recognition domain, a transmembrane domain, an intracellular co-stimulation signal transduction domain and a CD3 zeta signal transduction domain which are serially connected; the intracellular co-stimulation signal transduction domain mainly comprises a human TLR2 (Toll Like Receptor 2) intracellular domain. A GPC3 CAT T (Glypican 3 CAT T) cell prepared from the recombinant lentivirus has an intense cell killing effect on liver cancer cells, a Th1 cell factor can be highly expressed, a tumor killing effect caused by non-CAR T (Chimeric Antigen Receptor T) cell can be stimulated to the maximum extent, escape and potential reoccurrence risk of GPC 3-tumor cells can be effectively prevented, the tumor cells can be killed by T cells expressing the chimeric antigen receptor, normal tissue can be slightly damaged, a tumor immunosuppression micro environment can be broken through, and thus a relatively good treatment effect on solid tumor can be achieved.

A specific targeting peptide binding to glypican-3 can specifically binds to glypican-3 overexpressed in carcinoma cells and includes an amino acid sequence represented by SEQ ID NO:1 or some thereof. Glypican-3 is overexpressed in malignant tumors including hepatocellular carcinoma, melanoma, germ cell tumor, etc., and may be targeted in diagnosis and treatment of tumors by labeling the targeting peptide. A diagnosis using the specific peptide may detect even small tumors more accurately than conventional methods. A treatment method using the specific peptide may remove only carcinoma cells without harming other normal tissues.

The invention provides a method for evaluating postoperative recurrence risk of hepatocellular carcinoma patients prepared to be treated by radical operation of hepatocellular carcinoma on the basis of combined detection of cytokeratin 19 (CK19) and Glypican-3 (GPC3), tumor cells differentiation status and number of tumors as the indexes. According to the method, patients can be reasonably screened before operation so as to reduce metastasis and recurrence after radical operation of tumor. In addition, metastasis and recurrence risks after radical operation of hepatocellular carcinoma patients can be evaluated according to the method so as to further guide clinicians to carry out close monitoring and early treatment for cases with high risks of metastasis and recurrence.

The invention discloses a glypican-3 quantitative analysis kit. The glypican-3 quantitative analysis kit comprises a GPC3 standard product, an acridinium ester-marked glypican-3 antibody solution, and a nano-magnetic microsphere solution which is coupled with glypican-3 antibodies. The invention further provides a preparation method for the kit. The GPC3 nano-magnetic microsphere chemiluminescence immunoassay determination kit which takes acridinium ester as a luminescence marker provided by the invention has the characteristics of high sensitivity, wide linear range, high specificity, stable marker, low cost and the like; the detecting process of the kit is simple and quick; the glypican-3 can be detected by only requiring a micro sample.

The invention belongs to the field of molecular biology, and particularly discloses a method for detecting a CTC (circulating tumor cell) surface marker molecule GPC3 (glypican-3). The method comprises the following steps: performing erythrocyte splitting on blood, spreading and enriching all of left karyotes (mainly comprising CTCs and lymphocytes) on a nano-substrate for fixation by virtue of a nanotechnology, marking all the cells by virtue of a nucleus fluorescent dye DAPI, performing positive selection by virtue of a tumor immune fluorescent marker, i.e. a cytokeratin antibody anti-CK, and since a CTC surface has a specific expression of the GPC3, incubating all the cells by virtue of a GPC3 primary antibody, performing incubation by virtue of a secondary antibody marked with an FITC fluorescence group, and finally performing scanning by virtue of a high-throughput technology. Compared with the prior art, the detection method has the advantages of convenience, rapidness, economy, high sensitivity and specificity and capability of overcoming the defects of large sample amount requirement and incomplete reaction of GPC3 detection in the prior art.

Described herein is the identification of human monoclonal antibodies that bind GPC3 or heparan sulfate (HS) chains on GPC3 with high affinity. The antibodies described herein are capable of inhibiting HCC cell growth and migration. Provided are human monoclonal antibodies specific for GPC3 or HS chains on GPC3, including immunoglobulin molecules, such as IgG antibodies, as well as antibody fragments, such as single-domain VH antibodies or single chain variable fragments (scFv). Further provided are compositions including the antibodies that bind GPC3 or HS chains on GPC3, nucleic acid molecules encoding these antibodies, expression vectors comprising the nucleic acids, and isolated host cells that express the nucleic acids. Methods of treating cancer and / or inhibiting tumor growth or metastasis are also provided. Further provided are methods of detecting cancer in a subject and confirming a diagnosis of cancer in a subject.