Mesothelin antibody and anti-tumor activity due to effective methods

The present invention describes the use of phage display antibody engineering technology and synthetic peptide screening, to determine the human single-domain antibody against mesothelin SD1 and SD2. C- terminal SD1 recognizes human close to cell surface mesothelin (residues 539-588) conformational epitopes. SD2 binding full-length mesothelin. To study SD1 as potential therapeutic agents, generated recombinant human Fc (SD1-hFc) fusion protein. SD1-hFc proteins on tumor cell expressing mesothelin, in addition to the antibody - dependent cellular cytotoxicity (ADCC), but also exhibit a strong complement - dependent cytotoxicity (CDC). In addition, in nude mice in vivo, SD1-hFc protein having growth inhibitory significant tumor xenografts. SD1 and SD2 are a targeting tumors expressing mesothelin humanized single domain antibodies.