Soluble asparaginase-dextran conjugates show increased circulatory persistence and lowered antigen reactivity.
Oxidized dextrans of increasing molecular weight were bound covalently to Erwinia carotovora asparaginase. The resulting conjugates retained 50% of their enzyme activity and showed marked resistance to proteolysis by trypsin and chymotrypsin and inactivation by asparaginase-specific antibody. When tested in-vivo, the larger molecular weight conjugates showed prolonged circulatory survival in both immune and non-immune animals and failed to elicit full type III hypersensitivity or anaphylactic reactions when injected into sensitized guinea-pigs. Rabbits could tolerate multiple doses of the asparaginase conjugate without developing an immunity to the enzyme. A conjugate showing increased circulatory half-life and lowered antigen reactivity should have therapeutic potential.
T E
TE
Wileman
R L
RL
Foster
P N
PN
Elliott
D000818:Animals; D000941:Antigens; D001215:Asparaginase / Q000008:administration & dosage* / Q000097:blood / Q000276:immunology; D002626:Chemistry, Pharmaceutical; D002850:Chromatography, Gel; D003911:Dextrans; D004342:Drug Hypersensitivity / Q000209:etiology; D004355:Drug Stability; D005260:Female; D006168:Guinea Pigs; D007158:Immunologic Techniques; D007700:Kinetics; D008297:Male; D008970:Molecular Weight; D010447:Peptide Hydrolases; D011817:Rabbits; D012995:Solubility
D000941:Antigens; D003911:Dextrans; D010447:Peptide Hydrolases; D001215:Asparaginase