Engineering IL-2 to Give New Life to T Cell Immunotherapy

Annu Rev Med. 2021 Jan 27;72:281-311. doi: 10.1146/annurev-med-073118-011031. Epub 2020 Nov 6.


Interleukin-2 (IL-2) is integral to immune system regulation. Its opposing immunostimulatory and immunosuppressive actions make it an attractive therapeutic target for cancer and autoimmune diseases. A challenge in developing IL-2-directed anticancer therapies has been how to stimulate effector T cells (Teffs) without inducing regulatory T cells (Tregs) in the tumor microenvironment; conversely, IL-2 therapy for autoimmune diseases requires Treg induction without further stimulation of Teffs. High-dose IL-2 is approved for melanoma and renal cell carcinoma, but its therapeutic value is limited by a need for frequent dosing at specialist centers, its short half-life, severe toxicity, and a lack of efficacy in most patients. Re-engineered IL-2 therapeutics are designed to have longer in vivo half-lives, target specific IL-2 receptor conformations to stimulate specific T cell subsets, or localize to target tissues to optimize efficacy and reduce toxicity. We discuss recent studies that elucidate the potential of newly engineered IL-2-based therapeutics for cancer and autoimmune diseases.

Keywords: IL-2; autoimmunity; cancer; immunotherapy; interleukin-2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autoimmunity*
  • Bioengineering / methods*
  • Cell- and Tissue-Based Therapy / methods*
  • Humans
  • Immunotherapy / methods*
  • Interleukin-2 / immunology*
  • Neoplasms / immunology
  • Neoplasms / therapy*
  • T-Lymphocytes / immunology*


  • Interleukin-2