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 (cyclophosphamide and actinomycin D) and immunotherapy (TNF-α and macrophages) were evaluated on L1210 leukemia in mice. When given as single agents, both cyclophosphamide (CY), administered intraperitoneally 2 days after subcutaneous inoculation of leukemic cells, and actinomycin D (Act D), injected intratumorally (i.t.) 4 days following injection of leukemic cells, exerted therapeutic effects and prolonged mice survival. Unexpectedly, combination of CY and Act D did not result in prolongation of mice survival, due mainly to substantial cumulative toxic effects that led to death in several cases. Immunotherapy with TNF-α and Mφ, 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 leukemiabearing mice. This study indicates the potential of appropriate combinations of cytotoxic drugs with immunotherapy against neoplasia.