Abstract

Interleukin-2 (IL-2)-based immunotherapy, one of the earliest immunomodulatory approaches in cancer treatment, has played a pivotal role in activating cytotoxic T cells and natural killer (NK) cells. Nonetheless, the clinical application of IL-2 encounters obstacles such as a brief half-life, significant toxicity, and inadvertent stimulation of regulatory T cells. This review intends to scrutinize recent advancements in the development of engineered IL-2 derivatives, furnish a comprehensive overview of the cytokine's structural and functional attributes, evaluate clinical and preclinical research, and investigate novel strategies to mitigate adverse effects while enhancing therapeutic efficacy. Evidence suggests that emerging variants such as Bempegaldesleukin, THOR-707, and MDNA11 hold promise for safer and more efficacious treatments, with improved pharmacokinetics and targeted cellular activity. Furthermore, the utilization of computational methods and structural modeling as supplementary tools for predicting receptor interactions and biological outcomes is vital in the advancement of next-generation immunotherapies. Despite notable progress, considerable gaps in understanding persist regarding the molecular mechanisms and structure-function relationships of IL-2 derivatives, underscoring the need for more comprehensive and integrative research.

Keywords

immunotherapy, cancer, IL-2, cytokine engineering, IL-2 receptor