Modified pseudomonas exotoxin a

Abstract

The invention provides a Pseudomonas exotoxin A (PE) comprising an amino acid sequence having a substitution of one or more B-cell and/or T-cell epitopes. The invention further provides related chimeric molecules, as well as related nucleic acids, recombinant expression vectors, host cells, populations of cells, and pharmaceutical compositions. Methods of treating or preventing cancer in a mammal, methods of inhibiting the growth of a target cell, methods of producing the PE, and methods of producing the chimeric molecule are further provided by the invention.

1 - 42 . (canceled) 
     
     
         43 . A humanized anti-mesothelin antibody or antigen binding fragment thereof comprising a variable heavy chain domain sequence that is SEQ ID NO: 45 and a variable light chain domain sequence that is SEQ ID NO: 46. 
     
     
         44 . An isolated nucleic acid encoding the antibody or antigen binding fragment thereof of  claim 43 . 
     
     
         45 . An expression vector comprising the nucleic acid of  claim 44 . 
     
     
         46 . A host cell comprising the expression vector of  claim 45 . 
     
     
         47 . A method for producing a humanized anti-mesothelin antibody or antigen binding fragment thereof comprising: (i) culturing the host cell of  claim 46  in a medium; and (ii) purifying the antibody or fragment thereof from the cultured host cells. 
     
     
         48 . A composition comprising the antibody or antigen binding fragment of  claim 43  and a carrier. 
     
     
         49 . A chimeric molecule comprising the antibody or antigen binding fragment of  claim 43  conjugated or fused to a  Pseudomonas  exotoxin A.