Pseudomonas exotoxin a with less immunogenic b cell epitopes

A PE comprising an amino acid sequence comprising Formula I:

• FCS—R1m—R2p—R3n-PE functional domain III (Formula I)
• wherein:
• m, n, and p are, independently, 0 or 1;
• FCS comprises a furin cleavage sequence of amino acid residues, which sequence is cleavable by furin;
• R1 comprises 1 to 10 amino acid residues;
• R2 comprises 1 or more continuous amino acid residues of residues 285-364 of SEQ ID NO:
• 1;
• R3 comprises 1 or more continuous amino acid residues of residues 365-394 of SEQ ID NO:
• 1;
• and
• PE functional domain III comprises residues 395-613 of SEQ ID NO:
• 1 having a substitution of one or more of amino acid residues E420, D463, Y481, L516, R563, D581, D589, and K606 as defined by reference to SEQ ID NO:
• 1, with the proviso that when the amino acid residue at position 516 is substituted with alanine, at least one of amino acid residues E420, D463, Y481, R563, D581, D589, and K606 is substituted,
• wherein the PE has a further substitution of one or more amino acid residues within one or more B cell epitopes, and the further substitution for an amino acid within one or more B-cell epitopes is a substitution of, independently, one or more of amino acid residues E282, E285, P290, R313, N314, P319, D324, E327, E331, Q332, D403, D406, R412, R427, E431, R432, R458, D461, R467, R490, R505, R513, E522, R538, E548, R551, R576, Q592, and L597, as defined by reference to SEQ ID NO:
• 1, and
• wherein the PE optionally has a further substitution of one or more amino acid residues within one or more T-cell epitopes.