Chemo-immunotherapy of murine tumors using interleukin-2 (IL-2) and cyclophosphamide. IL-2 can facilitate or inhibit tumor growth depending on the sequence of treatment and the tumor type

Abstract

The antitumor effect of interleukin-2 (IL-2), alone and in combination with cyclophosphamide was assessed in mice with established sarcoma (MCA 105, H-2b), carcinoma (M109, H-2d) and T lymphoma (PIR-2, H-2b). Whereas administration of IL-2 alone (5 x 10(4)-10 x 10(4) U, i.p. twice daily, for 4-8 consecutive days) prolonged the survival of mice with the solid neoplasms, it enhanced tumor growth and decreased survival of mice with the lymphoma. In the PIR-2 lymphoma, no IL-2 receptor (TAC) could be detected, nor could we demonstrate IL-2 tumor growth stimulation in vitro. A synergistic therapeutic effect was achieved in mice with the solid tumors, but not in mice with the lymphoma, only when IL-2 was given 1-4 days after cyclophosphamide (100-200 mg/kg). Conversely, administration of IL-2 1-4 days prior to cyclophosphamide resulted, in all three tumor systems, in enhanced tumor growth and in decreased survival as compared with mice receiving cyclophosphamide alone. Similarly, treatment with IL-2 both before and after cyclophosphamide was less efficacious than a single course of IL-2 given afterwards. It is concluded that for maximal therapeutic efficacy, IL-2 should be administered following chemotherapy, and that certain tumors may respond adversely to IL-2 treatment.