Mesothelin antibodies and methods for eliciting potent antitumor activity

US9416190B2 · kind B2 · utility

Assignee

• The United States of America, as represented by the Secretary, Department of Health and Human Services · US

Inventors

• Mitchell Ho · Urbana, US
• Ira H. Pastan · Potomac, US
• Dimiter S. Dimitrov · Frederick, US
• Zhewei Tang · Rockville, US
• Mingqian Feng · Rockville, US
• Wei Gao · Rockville, US

Key dates

• Filing date: Sep 16, 2013
• Grant date: Aug 16, 2016
• Expiry date: Sep 16, 2033

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2333/705
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

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.