title: Tumor Targeting and Drug Delivery by Anthrax Toxin.
abstract: Anthrax toxin is a potent tripartite protein toxin from Bacillus anthracis. It is one of the two virulence factors and causes the disease anthrax. The receptor-binding component of the toxin, protective antigen, needs to be cleaved by furin-like proteases to be activated and to deliver the enzymatic moieties lethal factor and edema factor to the cytosol of cells. Alteration of the protease cleavage site allows the activation of the toxin selectively in response to the presence of tumor-associated proteases. This initial idea of re-targeting anthrax toxin to tumor cells was further elaborated in recent years and resulted in the design of many modifications of anthrax toxin, which resulted in successful tumor therapy in animal models. These modifications include the combination of different toxin variants that require activation by two different tumor-associated proteases for increased specificity of toxin activation. The anthrax toxin system has proved to be a versatile system for drug delivery of several enzymatic moieties into cells. This highly efficient delivery system has recently been further modified by introducing ubiquitin as a cytosolic cleavage site into lethal factor fusion proteins. This review article describes the latest developments in this field of tumor targeting and drug delivery.
authors.affiliation: BioMed X Innovation Center, Heidelberg 69120, Germany. bachran@bio.mx.
authors.forename: Christopher
authors.initials: C
authors.lastname: Bachran
authors.affiliation: Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. sleppla@niaid.nih.gov.
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Leppla
mesh_terms: D065767:Activation, Metabolic; D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D001692:Biological Transport; D004337:Drug Carriers; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006801:Humans; D000922:Immunotoxins / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D011355:Prodrugs / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism
chemical_list: D000942:Antigens, Bacterial; D000970:Antineoplastic Agents; D001427:Bacterial Toxins; D004337:Drug Carriers; D000922:Immunotoxins; D011355:Prodrugs; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors
keywords: cancer; drug delivery; immunotoxin; targeted toxin; tumor therapies