Interleukin 2-Based Fusion Proteins for the Treatment of Cancer

Figure 1

Properties of a next-generation IL-2-based fusion construct. A next generation IL-2-based fusion protein for cancer immunotherapy will encompass the criteria shown to overcome challenges associated with conventional IL-2 therapy. Due to the pleiotropic effects of IL-2 on different IL-2R-bearing immune cells, a biased agonist targeting CD8 T cells and NK cells bearing the intermediate affinity receptor, IL-2Rβγ, will promote antitumor immunity and limit expansion of immunosuppressive Tregs. Furthermore, traditional IL-2 therapy is limited by a short half-life, poor in vivo localization, and off-target activity which all contribute to adverse effects experienced by patients. Strategies that improve the pharmacokinetic and biodistribution profile of IL-2 will increase antitumor efficacy. Lastly, IL-2-based therapy delivered in combination with other treatment modalities will provide the best opportunity to overcome immunosuppression and immune escape that occurs. Tregs: T regulatory cells; TME: tumor microenvironment; dLN: draining lymph node; chemo: chemotherapy; rad: radiation; CPI: checkpoint inhibitor.