Interleukin-2 gene therapy of residual EL-4 leukaemia potentiates the effect of cyclophosphamide pretreatment

Experiments were designed to investigate a possible therapeutic role of interleukin-2 (IL-2) gene transfer in the model of murine (EL-4) leukaemia pretreated with cyclophosphamide. It has been found that i. p. pretreatment of the leukaemic mice with cyclophosphamide, followed by i. v. administration of irradiated cells, genetically engineered to produce IL-2 and used as a source of the cytokine (IR-IL-2 cells), cured a substantial percentage of the leukaemic mice. Neither treatment with cyclophosphamide nor administration of the IR-IL-2 cells alone had any significant therapeutic effect. Labelling of the EL-4 and IR-IL-2 cells with different fluorescent cell linkers followed by i. v. injection and detection of the labelled cells in cryostat sections of various organs has shown that both cell populations can be detected almost exclusively in the red pulp of the spleen, close to the white pulp nodules, thus providing the possibility of short-range local interactions among the IL-2-producing cells, IL-2-responsive defence effector cells and EL-4 leukaemia targets.