Interleukin-2 (IL-2) was the first approved immunotherapy to show efficacy in advanced cancer. 13–20% of patients with metastatic renal cell carcinoma and metastatic melanoma receiving high-dose IL-2 treatment showed objective clinical responses, some enduring for up to 20 years and more. However, the use of IL-2 immunotherapy was hampered by the short in vivo half-life of IL-2, dose-dependent toxicity and stimulation of immunosuppressive regulatory T cells. Recent efforts have explored the biology of IL-2 and its receptors to generate improved IL-2 formulations. Such IL-2 formulations provide targeted and potent stimulation of selected lymphocyte subsets, and they include IL-2/ anti-IL-2 monoclonal antibody complexes (briefly, IL-2 complexes), IL-2 muteins, and versions of IL-2 bound to polyethylene glycol or other molecules. In this article, we review the use of IL-2 for cancer immunotherapy, and discuss the preclinical and translational aspects of IL-2 complexes and their potential for the treatment of advanced cancer.

Keywords: