Abstract
Immunotoxins are genetically engineered fusion proteins of an antibody Fv fragment and a toxin from bacteria or plants, which function as anti-cancer therapeutics. Here, we describe a new generation of immunotoxins in which both proteins do not form a single fusion protein but are coupled specifically via cysteine-containing polyionic fusion peptides. The engineered Pseudomonas exotoxin PE38 was N-terminally fused to the peptide E(8)C. In combination with the disulfide-stabilized Fv fragment of the tumor-specific antibody B3, which was extended by the peptide R(8)CP, the fusion peptides ensured a specific and covalent coupling of the Fv fragment and the toxin. The resulting immunotoxin was as active and as specific as an immunotoxin consisting of a fusion protein of the same antibody fragment connected to the toxin.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / chemistry*
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ADP Ribose Transferases / genetics
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Antibodies, Monoclonal / genetics
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / metabolism
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Bacterial Toxins / chemistry*
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Bacterial Toxins / genetics
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Cell Death / drug effects
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Disulfides / chemistry*
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Drug Design*
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Exotoxins / chemistry*
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Exotoxins / genetics
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Immunoglobulin Fragments / chemistry
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Immunoglobulin Fragments / genetics
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Immunoglobulin Fragments / metabolism
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Immunotoxins / chemistry*
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Immunotoxins / genetics
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Immunotoxins / pharmacology*
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Models, Molecular
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Neoplasm Proteins / genetics*
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Neoplasm Proteins / immunology
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Neoplasm Proteins / metabolism
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Peptide Fragments / chemistry
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Peptide Fragments / metabolism*
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Plasmids
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Pseudomonas aeruginosa
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Pseudomonas aeruginosa Exotoxin A
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / pharmacokinetics
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Recombinant Fusion Proteins / pharmacology
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Structure-Activity Relationship
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Virulence Factors / chemistry*
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Virulence Factors / genetics
Substances
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Antibodies, Monoclonal
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Bacterial Toxins
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Disulfides
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Exotoxins
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Immunoglobulin Fragments
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Immunotoxins
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Neoplasm Proteins
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Peptide Fragments
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Recombinant Fusion Proteins
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Virulence Factors
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immunoglobulin Fv
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immunotoxin LMB-7
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ADP Ribose Transferases