Recombinant immunotoxins: protein engineering for cancer therapy.
Recombinant immunotoxins for cancer therapy are composed of the variable regions of 'cancer-specific' antibodies fused to truncated toxins that are usually derived from bacteria or plants. Protein engineering has been used to modify these molecules so that the toxin moiety by itself does not bind to normal human cells, but retains all other cytotoxic functions. The antibody moiety directs the toxin selectively to cancer cells, which are killed; cells that do not carry that particular cancer antigen are not recognized and are therefore spared. Many recombinant immunotoxins show a high degree of cytotoxic activity and specificity towards cancer cells cultured in vitro and have been shown to cause the regression of human tumor xenografts grown in mice. Clinical trials that are in progress will show whether these promising pre-clinical results can be translated into successful cancer therapy.
Brinkmann
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Laboratory of molecular biology, National Institutes of Health, National Cancer Institute, Bethesda, MD 20892-4255, USA. uli@helix.nih.gov
D036002:ADP Ribose Transferases; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000941:Antigens / Q000276:immunology; D001427:Bacterial Toxins; D005098:Exotoxins / Q000494:pharmacology; D006133:Growth Substances / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000276:immunology; D000922:Immunotoxins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism / Q000627:therapeutic use; D007938:Leukemia / Q000628:therapy; D008223:Lymphoma / Q000628:therapy; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000628:therapy*; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics* / Q000627:therapeutic use; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D000911:Antibodies, Monoclonal; D000941:Antigens; D001427:Bacterial Toxins; D005098:Exotoxins; D006133:Growth Substances; D007140:Immunoglobulin Fab Fragments; D007135:Immunoglobulin Variable Region; D000922:Immunotoxins; D011993:Recombinant Fusion Proteins; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A; C092978:immunotoxin LMB-7