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Annual Review of Medicine

Volume 72, 2021

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

Abstract

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.

Keyword(s): autoimmunity, cancer, IL-2, immunotherapy, interleukin-2
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2021-01-27
2024-04-25
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/content/journals/10.1146/annurev-med-073118-011031
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Engineering IL-2 to Give New Life to T Cell Immunotherapy
Annual Review of Medicine 72, 281 (2021); https://doi.org/10.1146/annurev-med-073118-011031
/content/journals/10.1146/annurev-med-073118-011031
/content/journals/10.1146/annurev-med-073118-011031
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  • Article Type: Review Article

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