期刊
ANNUAL REVIEW OF MEDICINE, VOL 72, 2021
卷 72, 期 -, 页码 281-311出版社
ANNUAL REVIEWS
DOI: 10.1146/annurev-med-073118-011031
关键词
interleukin-2; IL-2; autoimmunity; cancer; immunotherapy
资金
- Nektar Therapeutics
IL-2 plays a crucial role in immune system regulation and is a promising therapeutic target for cancer and autoimmune diseases, but challenges remain in balancing its immunostimulatory and immunosuppressive actions, as well as improving treatment efficacy while reducing toxicity. New IL-2 therapeutics are being developed to address these challenges and show potential in enhancing treatment outcomes.
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 halflife, 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.
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