Effects of stimulating interleukin -2/antiinterleukin -2 antibody complexes on renal cell carcinoma

Abstract

Background: Current therapies for advanced renal cell carcinoma (RCC) have low cure rates or significant side effects. It has been reported that complexes composed of interleukin (IL)-2 and stimulating anti-IL-2 antibody (IL-2C) suppress malignant melanoma growth. We investigated whether it could have similar effects on RCC. Methods: A syngeneic RCC model was established by subcutaneously injecting RENCA cells into BALB/c mice, which were administered IL-2C or phosphate-buffered saline every other day for 4 weeks. RCC size was measured serially, and its weight was assessed 4 weeks after RENCA injection. Immune cell infiltration into RCC lesions and spleen was assessed by flow cytometry and immunohistochemistry. Results: IL-2C treatment increased the numbers of CD8+ memory T and natural killer (NK) cells in healthy BALB/c mice (P < 0.01). In the spleen of RCC mice, IL-2C treatment also increased the number of CD8+ memory T, NK cells, and macrophages as compared to PBS-treated controls (P < 0.01). The number of interferon-γ- and IL-10-producing splenocytes increased and decreased, respectively after 4 weeks in the IL-2C-treated mice (P < 0.01). Tumor-infiltrating immune cells including CD4+ T, CD8+ T, NK cells as well as macrophages were increased in IL-2C-treated mice than controls (P < 0.05). Pulmonary edema, the most serious side effect of IL-2 therapy, was not exacerbated by IL-2C treatment. However, IL-2C had insignificant inhibitory effect on RCC growth (P = 0.1756). Conclusions: IL-2C enhanced immune response without significant side effects; however, this activity was not sufficient to inhibit RCC growth in a syngeneic, murine model.