PE-based immunotoxins. (A) The 2-chain disulfide-linked Fv of an antibody targeting a tumor-associated antigen is combined with the PE38 fragment of native PE to create an immunotoxin. (B) PE38 domains II and Ib. The sequences of domain II (residues 251-364) and domain Ib (residues 365-394) from PE38 are shown. Residue numbering is based on the amino acid sequence of native PE. Residues 365 to 380 from native PE (boxed) were deleted in the generation of PE38. Lysosomal protease cleavage sites, determined by N-terminal sequencing of fragments from B3(dsFv)-PE38 digests, are indicated by arrows adjacent to the designation of their corresponding band from SDS-PAGE analysis (Figure 2). Lysosomal protease cleavage sites occur between residues 260-261, 265-266, 297-298, 341-342, 342-343, 351-352, 352-353, 353-354, 364-381, 390-391, and 391-392. The furin cleavage site (279-280) is also indicated. The 11-residue furin-sensitive sequence in domain II from HA22-LR is shaded.