Cancer therapy with chemically modified enzymes. I. Antitumor properties of polyethylene glycol-asparaginase conjugates.
The covalent attachment of monomethoxypolyethylene glycol (PEG) to asparaginases from Escherichia coli and Vibrio succinogenes by new coupling methodology produced conjugates that are active, stable, without significant immune response, and with greatly extended plasma half-lives in mice. Therapeutic efficacies were greater for the PEG-asparaginases than for the unmodified asparaginases in mice infected with the L5178Y lymphosarcoma or the 6C3HED tumor. Large single doses of native or modified enzymes were more effective against tumors than the same amount of enzyme given in smaller doses over several days.
D000818:Animals; D000906:Antibodies / Q000032:analysis; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000276:immunology / Q000627:therapeutic use*; D001215:Asparaginase / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004797:Enzyme-Linked Immunosorbent Assay; D004800:Enzymes, Immobilized; D007940:Leukemia L5178 / Q000188:drug therapy*; D007942:Leukemia, Experimental / Q000188:drug therapy*; D008657:Metabolic Clearance Rate; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D011092:Polyethylene Glycols / Q000627:therapeutic use
D000906:Antibodies; D000970:Antineoplastic Agents; D004800:Enzymes, Immobilized; D011092:Polyethylene Glycols; C042705:pegaspargase; D001215:Asparaginase