Use of dimethylmyleran in adoptive chemoimmunotherapy of two murine leukemias

Abstract

Dimethylmyleran (DMM) is an antitumor agent that has minimal effects on immunity. In a study of its usefulness in adoptive chemoimmunotherapy, C57BL/6 mice inoculated on day 0 with C57BL/6 Friend virus-induced leukemia (FBL-3) were treated on day 5 with 12 mg DMM/kg [less than LD10 (lethal dose for 10% of mice)] plus C5BL/6 spleen cells. All untreated mice died, with a median survival time (MST) of 17 days. DMM alone or with nonimmune cells prolonged survival to day 20, and 3/53 mice survived beyond day 60. By contrast, 12/25 mice treated with DMM plus cells immune to FBL-3 were cured. Similar results were obtained in C57BL/6 mice with syngeneic Rauscher virus-induced leukemia (RBL-5). Untreated mice died, with an MST of 14 days. DMM alone or with nonimmune cells prolonged the MST to 21 and 26 days, respectively, and 3/26 and 6/28 mice were long-term survivors. However, 13/28 mice were cured by DMM plus cells immune to antigenically related FBL-3. Lethal irradiation of cells immune to FBL-3 abolished their efficacy. Finally, in contrast to the efficacy of sublethal DMM plus immune cells, an LD100 of DMM (20 mg/kg) plus hematopoietic reconstitution with nonimmune syngeneic cells was not effective against FBL-3 OR RBL-5. The results emphasized the critical role of immune cells in chemoimmunotherapy even when the drug used is nonimmunosuppressive.