Methods and Agents for the Diagnosis and Treatment of Hepatocellular Carcinoma
AssigneeChina Synthetic Rubber Corporation
InventorsKuo-Jang Kao, Andrew T. Huang
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Abstract
The present invention relates to methods of diagnosing, and methods of treating, hepatocellular carcinoma in a subject. The invention also relates to antagonists of PLVAP proteins, such as antibodies that specifically bind PLVAP proteins, as well as compositions and kits comprising antagonists of PLVAP proteins. The invention further relates to humanized antibodies that specifically bind PLVAP protein.
Claims42
A method of treating hepatocellular carcinoma (HCC) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one PLVAP antagonist, wherein the PLVAP antagonist inhibits an activity selected from the group consisting of tumor formation, tumor growth, tumor vascularization and tumor progression in the liver of the subject.
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A method of diagnosing hepatocellular carcinoma (HCC) in a subject, comprising:
- 1) detecting the level of a PLVAP gene product in a sample from the subject;
- and
- 2) determining that the level of the PLVAP gene product in the sample is increased relative to a control, wherein an increased level of the PLVAP gene product in the sample relative to the control is indicative of HCC in the subject,
- thereby diagnosing HCC in the subject.
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An isolated polypeptide that specifically binds SEQ ID NO:23, comprising an antibody variable domain selected from the group consisting of:
- 1) an antibody variable domain that comprises:
- a) a CDR1 consisting of SEQ ID NO:5;
- b) a CDR2 consisting of SEQ ID NO:6;
- and
- c) a CDR3 consisting of SEQ ID NO:7;
- 2) an antibody variable domain that comprises:
- d) a CDR1 consisting of SEQ ID NO:10;
- e) a CDR2 consisting of SEQ ID NO:11;
- and
- f) a CDR3 consisting of SEQ ID NO:12;
- and
- 3) a combination thereof.
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An isolated polypeptide that specifically binds SEQ ID NO:23, comprising at least one antibody variable domain selected from the group consisting of:
- 1) an antibody variable domain that comprises:
- a) a CDR1 consisting of SEQ ID NO:15;
- b) a CDR2 consisting of SEQ ID NO:16;
- and
- c) a CDR3 consisting of SEQ ID NO:17;
- 2) an antibody variable domain that comprises:
- d) a CDR1 consisting of SEQ ID NO:20;
- e) a CDR2 consisting of SEQ ID NO:21;
- and
- f) a CDR3 consisting of SEQ ID NO:22;
- and
- 3) a combination thereof.
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A pharmaceutical composition for the treatment of hepatocellular carcinoma in a mammalian subject, comprising at least one PLVAP antagonist and a pharmaceutically-acceptable carrier.
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A diagnostic kit for the detection of hepatocellular carcinoma in a mammalian subject, comprising a nucleic acid probe that specifically hybridizes to a PLVAP RNA transcript under conditions of high stringency, an antibody that specifically binds SEQ ID NO:23, or a combination thereof.
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An isolated antibody that specifically competes with monoclonal antibody KFCC-GY4 or monoclonal antibody KFCC-GY5 for binding to SEQ ID NO:23.
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Dependencies are inferred from the claim text.