Abstract
The novel HER2/neu-specific recombinant immunotoxin 4D5scFv-PE40 consisting of 4D5scFv antibody (targeting module) and Pseudomonas exotoxin A fragment (effector module) combined in a single polypeptide chain via a flexible linker has been expressed and purified. This immunotoxin conserves specificity and affinity that are characteristics of the parental antibody 4D5scFv and exhibits selective and strong cytotoxic effect against cancer cells overexpressing HER2/neu receptor. The results of the experiments both in vitro (in cell cultures) and in vivo (in tumor-bearing animals) demonstrate high potential of 4D5scFv-PE40 for targeted therapy of tumors overexpressing HER2/neu.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ADP Ribose Transferases / genetics
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Amino Acid Sequence
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Animals
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Antibody Specificity
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / immunology*
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Antineoplastic Agents / pharmacology*
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Bacterial Toxins / genetics
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Cell Line, Tumor
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Cell Survival / drug effects
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Exotoxins / genetics
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Female
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Humans
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Immunotoxins / chemistry
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Immunotoxins / genetics
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Immunotoxins / immunology*
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Immunotoxins / pharmacology*
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Mice
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Pseudomonas aeruginosa Exotoxin A
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Receptor, ErbB-2 / immunology*
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / immunology*
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Recombinant Fusion Proteins / pharmacology*
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Single-Chain Antibodies / genetics
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Virulence Factors / genetics
Substances
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Antineoplastic Agents
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Bacterial Toxins
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Exotoxins
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Immunotoxins
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Recombinant Fusion Proteins
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Single-Chain Antibodies
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Virulence Factors
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ADP Ribose Transferases
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Receptor, ErbB-2