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Efficacy of adjuvant interleukin-2 after excision of BALB/c fibrosarcomas
W J Gallagher1, S M Dubinett, H C Hoover
1Department of Surgery, Massachusetts General Hospital Cancer Center, Harvard Medical School, Boston.
Interleukin-2 (IL-2) has been evaluated as a therapeutic agent in a number of metastatic tumor systems. We hypothesized that administration of IL-2 might be more effective as adjuvant therapy in the presence of a greatly diminished tumor burden after tumor excision. In this BALB/c methylcholanthrene-induced sarcoma model, excision of 0.3 to 0.4 gm tumors results in local recurrence rates of 50% to 70%. Administration of human recombinant IL-2 at a dose of 50,000 units three times daily for 5 days to animals with established tumors resulted in 100% mortality. IL-2 administration started at the time of tumor implantation had no effect on tumor growth. Mice receiving adjuvant IL-2 at 50,000 units per dose after surgery had prolonged survival compared with controls (79% vs. 32%, p = 0.007); addition of concanavalin A-activated lymphocytes to IL-2 therapy did not enhance survival over that with IL-2 alone. Therapy with lower doses of adjuvant IL-2 on the same treatment schedule resulted in improved survival at doses as low as 5000 units (86% vs. 51% for controls, p = 0.003). Although the exact mechanism of this therapeutic effect has not been determined, IL-2 may act by a variety of mechanisms, including a decrease in the immunosuppressive effects of anesthesia and surgery, the generation of endogenous IL-2-activated effector cells, and the augmentation of efflux of circulating effector cells from peripheral blood into the site of surgically induced inflammation.
Interleukin-2 (IL-2) has been evaluated as a therapeutic agent in a number of metastatic tumor systems. We hypothesized that administration of IL-2 might be more effective as adjuvant therapy in the presence of a greatly diminished tumor burden after tumor excision. In this BALB/c methylcholanthrene-induced sarcoma model, excision of 0.3 to 0.4 gm tumors results in local recurrence rates of 50% to 70%. Administration of human recombinant IL-2 at a dose of 50,000 units three times daily for 5 days to animals with established tumors resulted in 100% mortality. IL-2 administration started at the time of tumor implantation had no effect on tumor growth. Mice receiving adjuvant IL-2 at 50,000 units per dose after surgery had prolonged survival compared with controls (79% vs. 32%, p = 0.007); addition of concanavalin A-activated lymphocytes to IL-2 therapy did not enhance survival over that with IL-2 alone. Therapy with lower doses of adjuvant IL-2 on the same treatment schedule resulted in improved survival at doses as low as 5000 units (86% vs. 51% for controls, p = 0.003). Although the exact mechanism of this therapeutic effect has not been determined, IL-2 may act by a variety of mechanisms, including a decrease in the immunosuppressive effects of anesthesia and surgery, the generation of endogenous IL-2-activated effector cells, and the augmentation of efflux of circulating effector cells from peripheral blood into the site of surgically induced inflammation.