Survival of leukemic cells in a dormant state following cyclophosphamide‐induced cure of strongly immunogenic mouse leukemia (DL811)

Abstract

The B-cell leukemia line, DL811, established in DDD mice, has been characterized by strong immunogenicity leading to occasional spontaneous cure with tumor dormancy. Cyclophosphamide (CY) is an available chemo-immunotherapeutic agent. The effects of CY on the cure and dormancy of DL811 leukemias were investigated. Simultaneous injection of DL811 cells and CY into athymic nude mice revealed that DL811 cells were sensitive to CY doses of 0.5 mg and more per mouse in a dose-related manner. A single dose of 1 mg CY on day 7 after DL811 cell inoculation was most curative of disseminated leukemias (cure rate: 50-80%) as compared with other single CY doses at different times. Cured mice were strongly immune to DL811 leukemias. This therapeutic modality had no curative effect in athymic nude mice. Relapses occurred occasionally in CY-cured mice and most relapsed tumors had the same surface phenotype as that of the DL811 leukemia. In comparison with DL811 leukemias, however, relapsed tumors were less sensitive to rejection by cured mice and less frequently cured by a single dose of 1 mg CY on day 7 of inoculation, implying that they changed in antigenicity and drug sensitivity. Whole-body irradiation of 400 rad gamma-rays to cured mice raised the incidence of relapses from 22.9 to 44.7% and that of deaths from relapses from 8.6 to 26.3%. Thus, leukemic cells may survive against host immune surveillance in a dormant state and relapse after changing their immunologic and chemotherapeutic natures. Lyt-2+, L3T4- T cells appeared to mediate host anti-tumor immunity to eradicate leukemic cells and maintain dormant state.