COMBINATION OF IMMUNOTHERAPY WITH CYCLOPHOSPHAMIDE ACTINOMYCIN-D CHEMOTHERAPY POTENTIATES ANTILEUKEMIC EFFECT AND REDUCES TOXICITY IN A L1210 LEUKEMIA MODEL IN MICE

The therapeutic effects of the combination of chemotherapy (cyclophosp hamide and actinomycin D) and immunotherapy (TNF-alpha and macrophages ) were evaluated on L1210 leukemia in mice. When given as single agent s, both cyclophosphamide (CY), administered intraperitoneally 2 days a fter subcutaneous inoculation of leukemic cells, and actinomycin D (Ac t D), injected intratumorally (i.t.) 4 days following injection of leu kemic cells, exerted therapeutic effects and prolonged mice survival. Unexpectedly, combination of CY and Act D did not result in prolongati on of mice survival, due mainly to substantial cumulative toxic effect s that led to death in several cases. Immunotherapy with TNF-alpha and M phi, injected i.t, on day 4 following inoculation of leukemic cells , did not give significant therapeutic effect, either when used alone or when used in conjunction. However, combination of chemotherapy and immunotherapy, including all four agents, produced a beneficial effect resulting in significant prolongation of the survival of leukemia-bea ring mice. This study indicates the potential of appropriate combinati ons of cytotoxic drugs with immunotherapy against neoplasia.