Entrapment of L-asparaginase in red blood cells. A strategy to improve treatment of acute lymphoblastic leukemia.
Autologous red blood cells were loaded with L-asparaginase and injected intravenously into monkeys. A single dose of 1850 IU/Kg suppressed plasma asparagine for 19 days compared to 10 days for the same dose injected free in solution. Rabbit antisera to asparaginase was used to passively immunize guinea-pigs. These animals were then challenged with RBC-entrapped asparaginase versus asparaginase free in solution. RBC entrapment allowed a ten fold greater dose of asparaginase before anaphylaxis became a problem. RBC entrapment prolongs the duration of action of asparaginase and offers protection against anaphylaxis. Clinical trial in patients with acute lymphoblastic leukemia is recommended.
D000707:Anaphylaxis / Q000517:prevention & control; D000818:Animals; D000917:Antibody Formation; D001215:Asparaginase / Q000008:administration & dosage* / Q000276:immunology; D004912:Erythrocytes; D006168:Guinea Pigs; D006207:Half-Life; D006801:Humans; D008253:Macaca mulatta; D014677:Pharmaceutical Vehicles
D014677:Pharmaceutical Vehicles; D001215:Asparaginase