Increased antitumor activity of Escherichia coli. L-asparaginase by modification with monomethoxypolyethylene glycol.
Escherichia coli L-asparaginase modified with monomethoxypolyethylene glycol, which has no ability to bind to the antibody and almost no immunogenicity, had a longer plasma half-life (32.9+/-2.5 hr) in normal mice than the native enzyme (3.35 +/- 0.45 hr). Preimmunization of mice with the native enzyme greatly shortened the plasma half-life of the native L-asparaginase (less than 0.1 hr) but did not change that of the modified L-asparaginase (32.2 +/- 2.1 hr). Treatment of mice bearing asparaginase-sensitive Gardner lymphoma (6C3HED) with L-asparaginases at various doses showed that the modified enzyme had a greater therapeutic effect than the native enzyme. In addition, preimmunization with the native enzyme prevented the antitumor activity of the native enzyme but did not affect the therapeutic efficacy of the modified L-asparaginase against the lymphoma.
D000818:Animals; D001215:Asparaginase / Q000097:blood / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000201:enzymology*; D008223:Lymphoma / Q000188:drug therapy*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008808:Mice, Inbred CBA; D009374:Neoplasms, Experimental / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000494:pharmacology*
D011092:Polyethylene Glycols; C028210:monomethoxypolyethylene glycol; D001215:Asparaginase