Mesothelin, A Differentiation Antigen Present On Mesothelium, Mesotheliomas, and Ovarian Cancers and Methods and Kits for Targeting the Antigen

Abstract

This invention relates to the discovery of a differentiation antigen termed mesothelin which is associated with mesotheliomas and ovarian cancers. Mesothelin is about 69 kD in its full-length form. The invention includes uses for the amino acid and nucleic acid sequences for mesothelin, recombinant cells expressing it, methods for targeting and/or inhibiting the growth of cells bearing mesothelin, methods for detecting the antigen and its expression level as an indication of the presence of tumor cells, and kits for such detection.

1 . An isolated nucleic acid encoding a chimeric molecule, said chimeric molecule comprising a targeting molecule and an effector molecule, wherein said targeting molecule specifically binds to a portion of mesothelin (SEQ ID NO.:2) that is not bound by monoclonal antibody K1, a monoclonal antibody secreted by a hybridoma deposited as ATCC Accession No. HB 10570. 
     
     
         2 . The isolated nucleic acid of  claim 1 , wherein said effector molecule is a cytotoxin or a drug. 
     
     
         3 . The isolated nucleic acid of  claim 1 , wherein said effector molecule is a cytotoxin. 
     
     
         4 . The isolated nucleic acid of  claim 3 , wherein said cytotoxin is selected from the group consisting of a modified  Pseudomonas  exotoxin A, ricin, abrin and a modified Diphtheria toxin. 
     
     
         5 . The isolated nucleic acid of  claim 1 , further wherein said nucleic acid is operably linked to an expression control sequence. 
     
     
         6 . A transfected cell comprising a recombinant nucleic acid encoding a chimeric molecule, said chimeric molecule comprising a targeting molecule and an effector molecule, wherein said targeting molecule specifically binds to a portion of mesothelin (SEQ ID NO.:2) that is not bound by monoclonal antibody K1, a monoclonal antibody secreted by a hybridoma deposited as ATCC Accession No. HB 10570. 
     
     
         7 . The transfected cell of  claim 6 , wherein said effector molecule is a cytotoxin or a drug. 
     
     
         8 . The transfected cell of  claim 7 , wherein said effector molecule is a cytotoxin. 
     
     
         9 . The transfected cell of  claim 7 , wherein said cytotoxin is selected from the group consisting of a modified  Pseudomonas  exotoxin A, ricin, abrin and a modified Diphtheria toxin. 
     
     
         10 . The transfected cell of  claim 6 , wherein said cell is an  E. coli  cell.