Advances in antibody-directed enzyme prodrug therapy.
Antibody-directed enzyme prodrug therapy has demonstrated feasibility as a treatment for cancer. Numerous prodrug/drug systems have been developed for activation by a variety of enzymes and although many have shown potential in preclinical studies, so far only one system has progressed to the clinic. Clinical studies have identified issues that were not readily apparent in xenograft models, however, these have not been addressed in the development and testing of new prodrugs. The issue of immunogenicity arising from the use of non-human enzymes has also been a major hurdle. The development of recombinant fusion proteins provides reproducible and effective antibody-enzyme products that retain the necessary specificity for prodrug activation. Advances in molecular, structural and systems biology, in combination with bioinformatics, have allowed these molecules to be readily manipulated to provide the desired characteristics.
Department of Oncology, Royal Free & University College Medical School, University College London, Hampstead Campus, Rowland Hill Street, London NW3 2PF. surinder.sharma@ucl.ac.uk
Surinder K
SK
Sharma
Kenneth D
KD
Bagshawe
Richard H J
RH
Begent
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology; D016503:Drug Delivery Systems; D004798:Enzymes / Q000008:administration & dosage* / Q000378:metabolism; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D011355:Prodrugs / Q000008:administration & dosage / Q000627:therapeutic use*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D004798:Enzymes; D011355:Prodrugs; D011993:Recombinant Fusion Proteins