Combined chemoimmunostimulation therapy against murine leukemia.

Abstract

The effect of combining chemotherapy and immunostimulation against a murine lymphoid leukemic line designated as LSTRA was investigated. Inoculation of 1 × 104 ascites cells s.c. resulted in the death of all animals within 12 to 15 days. Treatment of infected mice with 1,3-bis(2-chloroethyl)-1-nitrosourea, 20 mg/kg, increased the range of death to 20 to 28 days with a significant number of long-term survivors (12%). The parameters utilized to determine the appearance of disease, induction of remission, and relapse following drug therapy were based on the bioassay of donor tissue at specified time intervals. When Bacillus Calmette-Guerin and Corynebacterium granulosum were used following 1 administration of 1,3-bis(2-chloroethyl)-1-nitrosourea, 20 mg/kg, a high percentage of long-term survivors occurred in contrast to the groups of animals treated with immunostimulants or drug alone. The most important variable in these studies was the time in which immunostimulants were given following drug therapy. C. granulosum , when given 3 days after 1,3-bis(2-chlorethyl)-1-nitrosourea therapy, resulted in 76% complete remissions, while B. Calmette-Guerin was most effective 12 days after drug treatment, yielding approximately 68% long-term survivors. The implications of these results to cancer therapy are discussed.