Developments with targeted enzymes in cancer therapy.
Cancer therapy based on the delivery of enzymes to tumour sites has advanced in several directions since antibody-directed enzyme/prodrug therapy was first described. It has been shown that methoxypolyethylene glycol (MPEG) can be used to deliver enzyme to a variety of solid tumours. MPEG-enzyme conjugates show reduced immunogenicity and may allow repeated treatment with enzymes of bacterial origin. Enzyme delivery to tumours by polymers can be used to convert a low toxicity prodrug to a potent cytotoxic agent. An example of such a prodrug is CB1954, which can be activated by a human enzyme in the presence of a cosubstrate. Tumour-located enzymes can also be used in conjunction with a combination of antimetabolites and rescue agents. The rescue agent protects normal tissue but is degraded at cancer sites by the enzyme, thus deprotecting the tumour and allowing prolonged antimetabolite action.
Bagshawe
K D
KD
Department of Medical Oncology, Imperial College of Medicine, Charing Cross campus London, W6 8RP, UK. k.bagshawe@cxwms.ac.uk
Sharma
S K
SK
Burke
P J
PJ
Melton
R G
RG
Knox
R J
RJ
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001388:Aziridines / Q000627:therapeutic use; D004337:Drug Carriers / Q000627:therapeutic use; D057487:Enzyme Therapy; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011355:Prodrugs / Q000378:metabolism / Q000627:therapeutic use*; D011623:gamma-Glutamyl Hydrolase / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001388:Aziridines; D004337:Drug Carriers; D018796:Immunoconjugates; D011355:Prodrugs; D011092:Polyethylene Glycols; C100099:tretazicar; C028210:monomethoxypolyethylene glycol; D011623:gamma-Glutamyl Hydrolase