Therapeutic properties of a new glutaminase-asparaginase preparation and the influence of the lactate dehydrogenase-elevating virus.

A new enzyme termed GA: 1.2, possessing approximately equal amounts of glutaminase and asparaginase activity, has antitumor activities against cancers other than leuke mia, thus enlarging the potential for cancer therapy by amino acid deprivation. When tested against the asparagine-dependent EARAD-1 leukemia in the presence of the láclatedehydrogenase-elevating virus (LDH-virus), striking tumor regression was obtained. This asparagine-dependent mouse tumor was used as a model to study the basic mech anism of the therapeutic action of the enzyme and its in fluence upon various plasma amino acids in the presence and absence of the LDH-virus. At doses of 150 lU/kg and higher, both plasma glutamine and asparagine were de pleted to undetectable levels (less than 1 nmole/ml) when the virus was present but not in its absence. Tumor regres sion was correlated with asparagine and glutamine deple tion in the plasma. Although there were no measurable dif ferences in the plasma glutamine and asparagine depletion below 1 nmole/ml as a function of increasing enzyme dose, both glutamic and aspartic acids increased systematically with dose. The plasma half-life of GA: 1.2 is 1 to 2 hr in normal mice, but was increased to 12 to 18 hr when mice were infected with the LDH-virus. Thus, the presence of the LDH-virus in the host is necessary for expression of the therapeutic capabilities of the enzyme preparation on this and presumably other mouse tumor systems.