Anticancer Cytokines: Biology and Clinical Effects of Interferon-α2, Interleukin (IL)-2, IL-15, IL-21, and IL-12

Efforts over nearly four decades have focused on ways to use cytokines to manipulate the host immune response towards cancer cell recognition and eradication. Significant advances were achieved with interleukin-2 (IL-2) and interferon-α (IFN-α), primarily in the treatment of patients with melanoma and renal cell carcinoma. However, the utility of other cytokines showing promise in the preclinical setting has not been established largely because of toxicity, the complex functionality of each cytokine and the difficulty mimicking in preclinical models the human environment. Here, we review the basic biology and the clinical experiences with IFN-α, IL-2, IL-15, IL-21, and IL-12. We will also review ongoing clinical trials and discuss future directions including potential use of cytokines in combination with other effective immunotherapy approaches that have come of age in recent years.