Antileukemic effects of recombinant human tumor necrosis factor alpha (rh-TNF alpha) with cyclophosphamide or methotrexate on leukemia L1210 and leukemia P388 in mice.

We investigated the influence of recombinant human tumor necrosis factor alpha (rh-TNF alpha) administered as a single agent or in combination with cyclophosphamide (CY) or methotrexate (MTX) on the survival time of mice inoculated with lymphoblastic leukemia L1210 or lymphatic leukemia P388. The median survival time of leukemia L1210 bearing mice treated with rh-TNF alpha at doses ranging from 200 to 275 g/kg in daily i.p. injections was longer than that of control animals. Groups of mice with leukemia L1210 receiving rh-TNF alpha combined with either MTX or CY lived longer than animals treated with these agents individually. We observed only slight prolongation of life of animals inoculated with this tumor and treated with rh-TNF alpha at dose of 800 micrograms/kg in four injections on 2, 4, 6 and 8 day of experiment, and no effect when rh-TNF alpha was administered at dose of 200 or 400 micrograms/kg at the same treatment regime. In contrast no significant differences in lifetime were obtained from either simultaneous or sequential treatment of mice bearing leukemia P388. Groups of mice with this tumor treated with rh-TNF alpha in conjunction with either MTX or CY lived longer than controls, or rh-TNF alpha singly treated mice, but their survivals were not significantly prolonged compared with mice receiving cytostatics alone.