Why toxins!
Toxins are potent cytotoxic proteins which gain access to the interior of mammalian cells by receptor-mediated endocytosis. However, the trafficking pathways within mammalian cells are complex and toxins must be processed to active forms while avoiding degradation by the lysosomal system. Once delivered to an appropriate intracellular location, the active toxin fragment translocates to the cell cytosol and inhibits protein synthesis. Chimeric toxins are constructed by removing the toxins natural binding domain and replacing it with an antibody or cell-binding ligand that redirects cell killing activity to cancer cells. Gaining an understanding of how toxins manoeuvre within cells is vital for improving the effectiveness of chimeric toxins.
Fitzgerald
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Laboratory of Molecular Biology, DBS, NCI, Bethesda, MD 20892-4255, USA.
D036002:ADP Ribose Transferases; D000818:Animals; D001427:Bacterial Toxins / Q000494:pharmacology; D002478:Cells, Cultured; D004167:Diphtheria Toxin / Q000494:pharmacology; D005098:Exotoxins / Q000494:pharmacology; D005544:Forecasting; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000628:therapy; D009374:Neoplasms, Experimental / Q000628:therapy; D011994:Recombinant Proteins / Q000378:metabolism / Q000494:pharmacology; D012276:Ricin / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014118:Toxins, Biological / Q000494:pharmacology; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A
D036002:ADP Ribose Transferases; D001427:Bacterial Toxins; D004167:Diphtheria Toxin; D005098:Exotoxins; D000922:Immunotoxins; D011994:Recombinant Proteins; D012276:Ricin; D014118:Toxins, Biological; D037521:Virulence Factors; D000097668:Pseudomonas aeruginosa Exotoxin A