extended half-life interleukin-2

Extended half-life interleukin-2 (IL-2) refers to a category of engineered cytokine therapeutics designed to improve the pharmacokinetic profile and therapeutic index of recombinant human IL-2 (aldesleukin). Native IL-2 has an extremely short serum half-life, necessitating frequent high-dose administration that often leads to severe systemic toxicities such as vascular leak syndrome. Extended half-life variants are developed using strategies such as PEGylation, fusion to Fc domains or human serum albumin, or other protein engineering techniques to prolong circulation. Many of these molecules are also engineered to be "biased" agonists, meaning they have reduced affinity for the IL-2Rα (CD25) subunit to avoid the activation of immunosuppressive regulatory T cells (Tregs), while maintaining or enhancing affinity for the IL-2Rβγ complex on effector T cells and natural killer (NK) cells. In the context of neuro-oncology, these agents are being investigated for their ability to reverse systemic immunosuppression and synergize with checkpoint inhibitors like anti-PD-1 in treating glioblastoma.

Other names

extended half-life IL-2long-acting IL-2engineered IL-2extended 1/2-life IL-2