Antibody-directed enzyme prodrug therapy (ADEPT) for cancer.
Antibody-directed enzyme prodrug therapy (ADEPT) aims to restrict the cytotoxic action to tumour sites. The obstacles to achieve this were recognised at the outset, but time and experience have given these better definition. The development of fusion proteins has provided the means of making consistent antibody-enzyme constructs on an adequate scale, and glycosylation has provided the means to control the clearance of enzyme from non-tumour sites. Human enzymes have yet to be tested in a clinical setting, and there are pointers indicating that the immunological response to foreign enzymes can be overcome. The relatively small number of purpose-designed prodrugs tested so far leaves this an area ripe for further development. The ongoing iterative process between preclinical and clinical studies is critical to achieving the objective.
Bagshawe
Kenneth D
KD
Department of Oncology, Royal Free & University College Medical School, University College London, UK.
Sharma
Surinder K
SK
Begent
Richard H J
RH
D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000096:biosynthesis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000276:immunology / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001426:Bacterial Proteins / Q000235:genetics / Q000627:therapeutic use; D045744:Cell Line, Tumor / Q000187:drug effects; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D057487:Enzyme Therapy; D004798:Enzymes / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics; D006031:Glycosylation; D006207:Half-Life; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics / Q000627:therapeutic use; D007141:Immunoglobulin Fc Fragments / Q000008:administration & dosage / Q000737:chemistry / Q000235:genetics / Q000627:therapeutic use*; D008322:Mammals / Q000235:genetics; D051379:Mice; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011499:Protein Processing, Post-Translational; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
D000888:Antibodies, Anti-Idiotypic; D000951:Antigens, Neoplasm; D000970:Antineoplastic Agents; D001426:Bacterial Proteins; D004798:Enzymes; D018796:Immunoconjugates; D007141:Immunoglobulin Fc Fragments; D011355:Prodrugs; D011993:Recombinant Fusion Proteins