The T-Cell Growth Factor Interleukin-2, Which Is Occasionally Targeted by Autoantibodies, Qualifies as Drug for the Treatment of Allergy, Autoimmunity, and Cancer: Collegium Internationale Allergologicum (CIA) Update 2024

Interleukin(IL)-2 was originally characterized as an important T-cellular growth factor but later on, turned out to be a pivotal homeostatic factor for the establishment and maintenance of both natural(n)Treg and peripheral(p)Treg. In this review, it was aimed to connect the peculiar structural and functional aspects of IL-2 to the innovative advancements in tailoring its multifaceted functional behavior for targeting various IL-2 receptor types. The article includes detailed descriptions of modified versions of IL-2, obtained by either mutating or fusing IL-2 to heterologous molecules or by forming IL-2/(monoclonal) antibody complexes (IL-2C), and discusses their functional implications for addressing such heterologous pathological conditions in cancer, autoimmunity, and allergy. Additionally, this review sheds light on the underexplored contribution of autoantibodies to the endogenous regulation of IL-2 within the realms of both health and disease. The ongoing efforts to fine-tune IL-2 responses through antibody-dependent targeting or molecular engineering offer considerable translational potential for the future utility of this important cytokine.

Automated summary

This review discusses the peculiar structural and functional aspects of interleukin (IL)-2, and the innovative advancements in tailoring its multifaceted functional behavior for targeting different IL-2 receptor types. The article also introduces modified versions of IL-2, obtained by mutation, fusion with heterologous molecules, or forming complexes with antibodies, and discusses their implications in cancer, autoimmunity, and allergy. Furthermore, the review sheds light on the contribution of autoantibodies to the regulation of IL-2 in both health and disease. Ongoing efforts to fine-tune IL-2 responses through antibody-dependent targeting or molecular engineering offer promising translational potential for this important cytokine in the future.