A chimeric molecule targeting mesothelin comprising a fusion polypeptide having the formula M-L1-FCS-FL-functional Pseudomonas exotoxin domain III characterized in that the flexible linker consists of from 3 to 8 continuous amino acid residues selected independently from glycine and serine, wherein (a) M is an antibody which specifically binds to mesothelin, or a fragment thereof that specifically binds mesothelin; (b) L1 consists of from 1 to 10 continuous amino acid residues; (c) FCS is a furin cleavage site consisting of continuous amino acid residues capable of being cleaved by furin; (d) Functional PE domain III consists of continuous amino acid residues identical in sequence to SEQ ID NO: 1 from position 395 to 613, optionally comprising (i) a substitution of one or more residues corresponding to 609-613 of SEQ ID NO:1, (ii) a substitution of glycine, alanine, valine, leucine, or isoleucine for arginine at a position corresponding to position 490 of SEQ ID NO:1, (iii) a substitution of, independently, alanine, glycine, serine or glutamine in place of one or more residues corresponding to residues D403,R412, R427, E431, R458, D461, R505, E522, R538, R551, R576, and L597 of SEQ ID NO:1 (iv) a substitution of, independently, alanine, glycine or serine in place of one or more residues corresponding to residues D406, R432, R467, R490, R513, E548, K590, and Q592 of SEQ ID NO: 1, or (v) a combination of any of (i)-(iv). (a) M is an antibody which specifically binds to mesothelin, or a fragment thereof that specifically binds mesothelin; (b) L1 consists of from 1 to 10 continuous amino acid residues; (c) FCS is a furin cleavage site consisting of continuous amino acid residues capable of being cleaved by furin; (d) Functional PE domain III consists of continuous amino acid residues identical in sequence to SEQ ID NO: 1 from position 395 to 613, optionally comprising (i) a substitution of one or more residues corresponding to 609-613 of SEQ ID NO:1, (ii) a substitution of glycine, alanine, valine, leucine, or isoleucine for arginine at a position corresponding to position 490 of SEQ ID NO:1, (iii) a substitution of, independently, alanine, glycine, serine or glutamine in place of one or more residues corresponding to residues D403,R412, R427, E431, R458, D461, R505, E522, R538, R551, R576, and L597 of SEQ ID NO:1 (iv) a substitution of, independently, alanine, glycine or serine in place of one or more residues corresponding to residues D406, R432, R467, R490, R513, E548, K590, and Q592 of SEQ ID NO: 1, or (v) a combination of any of (i)-(iv). (i) a substitution of one or more residues corresponding to 609-613 of SEQ ID NO:1, (ii) a substitution of glycine, alanine, valine, leucine, or isoleucine for arginine at a position corresponding to position 490 of SEQ ID NO:1, (iii) a substitution of, independently, alanine, glycine, serine or glutamine in place of one or more residues corresponding to residues D403,R412, R427, E431, R458, D461, R505, E522, R538, R551, R576, and L597 of SEQ ID NO:1 (iv) a substitution of, independently, alanine, glycine or serine in place of one or more residues corresponding to residues D406, R432, R467, R490, R513, E548, K590, and Q592 of SEQ ID NO: 1, or (v) a combination of any of (i)-(iv).