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.