A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.

The clinical use of interleukin-2 (IL-2) for cancer immunotherapy is limited by severe toxicity. Emerging IL-2 therapies with reduced IL-2 receptor alpha (IL-2Rα) binding aim to mitigate toxicity and regulatory T cell (Treg) expansion but have had limited clinical success. Here, we show that IL-2Rα engagement is critical for the anti-tumor activity of systemic IL-2 therapy. A "non-α" IL-2 mutein induces systemic expansion of CD8

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Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests All authors are employees of Regeneron Pharmaceuticals, Inc. and may hold stock or stock options in the company. J.W., T.Z., E.S., and J.C.L. are inventors on US patent US11725034B2; “IL2 agonists and methods of uses thereof”. J.W., N.B., T.Z., J.C.L., S.D., E.S., and E.U. are inventors on a pending US patent application (US20220402989A1; “IL2-based therapeutics and methods of uses thereof”). D.J.D. and J.W. are inventors on a pending US patent application (US20240148867A1; “Methods of treating cancer with a combination of adoptive cell therapy and a targeted immunocytokine”).