Therapeutic efficacy of asparaginase encapsulated in intact erythrocytes

Abstract

Asparaginase has been encapsulated in intact erythrocytes by a gentle loading technique. The loaded cells were found to survive removal by the recticuloendothelial system when returned to the circulation of mice. In addition the enzyme removed all detectable asparagine from the plasma in vivo for at least two weeks after the injection of the loaded cells. In vitro evidence suggested that the asparagine entered the cell and was metabolised by the loaded enzyme in situ. No evidence was found to suggest that the enzyme left the cell. When the encapsulated asparaginase was tested against the 6C3HED tumour in C3H mice the encapsulated preparation was superior to the free enzyme in treating the tumour and was the only treatment to produce 'cured' mice. Encapsulated asparaginase also lowered glutamine levels both in vivo and in vitro. The possibility that LDH virus was responsible for the excellent results obtained with the encapsulated enzyme was investigated and eliminated.