The United States of America, as Represented by the Secretary, Department of Health and Human Services

Mingqian Feng

Dimiter Stanchev Dimitrov

Mitchell Ho

Wei Gao

Ira H Pastan

Zhewei Tang

Heungnam Kim

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.

Human monoclonal antibodies specific for glypican-3 and use thereof

Described herein is the use of phage display antibody engineering technology and synthetic peptide screening to identify SD1 and SD2, human single-domain antibodies to mesothelin. SD1 recognizes a conformational epitope at the C-terminal end (residues 539-588) of human mesothelin close to the cell surface. SD2 binds full-length mesothelin. To investigate SD1 as a potential therapeutic agent, a recombinant human Fc (SD1-hFc) fusion protein was generated. The SD1-hFc protein exhibits strong complement-dependent cytotoxicity (CDC), in addition to antibody-dependent cellular cytotoxicity (ADCC), against mesothelin-expressing tumor cells. Furthermore, the SD1-hFc protein causes significant tumor growth inhibition of tumor xenografts in nude mice. SD1 and SD2 are the first human single-domain antibodies targeting mesothelin-expressing tumors.

Mesothelin antibodies and methods for eliciting potent antitumor activity

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Rockville, MD, United States of America

Mingqian Feng