We have studied the effect of active specific immunization (ASI) on the antitumor response induced by locoregional, low-dose
interleukin-2 (IL-2)
therapy. On day 0, mice were injected i.p. with viable, syngeneic
tumor cells and with irradiated
tumor cells (ASI). Low-dose
IL-2 treatment was given i.p. for 5 consecutive days. ASI led to extended survival in two out of seven models tested. In these two models, enhanced efficacy was observed when both ASI and
IL-2 were administered. In the five models in which ASI had no therapeutic value, ASI +
IL-2 treatment was no more effective than
IL-2 therapy. In the SL2
lymphoma model, use of ASI prior to
IL-2 therapy given as early as days 1-5 led to at least 60% cure, whereas
IL-2 therapy without ASI was only effective when administered after day 9. In the P815
mastocytoma model, however, ASI,
IL-2, and the combination caused negative (suppressive) effects when administered on days 6-10.
IL-2 administered on days 6-10 was therapeutically effective in this model when mice were treated with
cyclophosphamide on day 6. In both the SL2 and the P815
tumor models, cured mice were specifically immune. The positive and negative effects observed were not due to the increased number of cells injected (non-specific
inflammation) nor to possible antigenic alteration of the ASI cells by irradiation, as ASI with fragmented
tumor cells was also effective in inducing synergy. Investigations into the underlying mechanism indicated that CD4+ cells play an important role. In total, the results indicate that ASI may be a good supplement to locoregional
IL-2 treatment if care is taken to alleviate immunosuppressive activities.