COMPARISON OF THE POTENTIAL THERAPEUTIC EFFECTS OF INTERLEUKIN-2 OR INTERLEUKIN-4 SECRETION BY A SINGLE TUMOR

Engineering of a variety of rodent tumour cells to secrete either inte rleukin 2 (IL-2), or interleukin 4 (IL-4), has been demonstrated to re duce their tumorigenicity. However the mechanisms of action of secrete d IL-2 and IL-4 have not been compared in a single rodent tumour. Here we demonstrate that the weakly immunogenic murine fibrosarcoma FS29 h ad reduced growth rate and in some cases was rejected by syngeneic ani mals, when modified to secrete either IL-2 or IL-4, but not IL-5. Immu nohistochemical analysis of tumour nodules undergoing regression showe d stimulation of a largely lymphocytic infiltrate by IL-2 and a macrop hage and granulocyte infiltrate, with a small number of lymphocytes by IL-4. Indeed, secretion of low levels of IL-2 and IL-4 in combination resulted in optimal rejection, suggesting that the two cytokines migh t mobilise different and complementary effector cell mechanisms. Both IL-2 and IL-4-secreting cells failed to induce the rejection of admixe d, unmodified FS29 cells. The loss of cytokine secreting cells from su ch admixtures occurred more rapidly for IL-2-secreting cells. Injectio n of IL-4-secreting, but not IL-2-secreting FS29 cells could protect m ice from a delayed challenge with unmodified FS29 cells. These data su ggest that IL-4 secretion stimulates the better long-term host anti-tu mour response.