Increasing the time interval between doses of anti-CD137 and IL-2-Fc failed to alleviate the severe toxicity of the combination treatment, while administration of lower doses of anti-CD137/IL-2-Fc lowered the degree of toxicity but also reduced the efficacy in slowing tumor progression (Fig. 1a–c, Supplementary Fig. 1a–c), suggesting that anti-tumor efficacy and toxicity were linked in this systemic therapy. The gene discussed is IL2; the disease is neoplasm.