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

Int Arch Allergy Immunol. 2024;185(3):286-300. doi: 10.1159/000533677. Epub 2023 Dec 12.

Abstract

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.

Keywords: Allergy; Autoimmunity; Cancer; IL-2C; IL-2R; Interleukin-2; Muteins; T cell growth factor; T regulatory cells; Treg.

Publication types

  • Review

MeSH terms

  • Autoantibodies
  • Autoimmunity
  • Humans
  • Hypersensitivity* / drug therapy
  • Interleukin-2 / metabolism
  • Interleukin-2 / therapeutic use
  • Interleukins
  • Neoplasms* / drug therapy
  • T-Lymphocytes, Regulatory

Substances

  • Interleukin-2
  • Autoantibodies
  • Interleukins

Grants and funding

This work was supported by the Medical University of Vienna and the Danube Allergy Research Cluster (Danube ARC) supported by the State of Lower Austria.