Deoxyribonuclease I (DNAse I). A novel approach for targeted cancer therapy.
A number of phosphodiesterases, some of which possess additional biological activities (e.g., antitumor, immunosuppressive, and so on), have been considered for use in targeted tumor therapy. We propose Deoxyribonuclease I (DNase I), a compact, monomeric enzyme, as a very attractive candidate for targeting to tumor cells. Only a small amount of enzyme targeted to a cell needs to enter the nucleus in order to degrade the chromosomal DNA, making a cell incapable of further replication. We describe preliminary data on the construction of a potent single-chain antibody (scFv) immunotoxin based on bovine pancreatic DNAse I. The use of a mammalian enzyme should be much less toxic and less immunogenic than current immunotoxins and may expand the current limits of immunotoxin therapy.
Linardou
H
H
Tumour Targeting Laboratory, Imperial Cancer Research Fund, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Deonarain
M P
MP
Spooner
R A
RA
Epenetos
A A
AA
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D003850:Deoxyribonuclease I / Q000627:therapeutic use*; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use*; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000628:therapy*
D000922:Immunotoxins; D003850:Deoxyribonuclease I