Detection of early and delayed antitumor effects following curative adoptive chemoimmunotherapy of established leukemia

Abstract

Advanced disseminated leukemia can be successfully eradicated by treatment with a combination of noncurative nonlethal chemotherapy plus adoptively transferred immune cells. The time course of tumor elimination following such therapy was examined by bioassay for tumor of peripheral blood and spleen cells from treated mice. Curative treatment with adoptive chemoimmunotherapy did not immediately eliminate all leukemia. Bioassay of cells from treated mice, rather, demonstrated that, following the initial tumor lysis mediated by the chemotherapy and immune cells, a period of tumor regrowth lasting several weeks preceded ultimate tumor eradication. This transient tumor regrowth detectable by bioassay never became clinically evident in the treated mice. However, immunosuppression of mice two weeks after treatment with adoptive chemoimmunotherapy resulted in recurrence of lethal tumor. The results suggest that tumor elimination following curative adoptive chemoimmunotherapy is biphasic and that the efficacy of therapy may be subject to positive and/or negative influences over a prolonged time period.