{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["5(10)"],"submitter":["Wu J"],"funding":["Regeneron Pharmaceuticals"],"pubmed_abstract":["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<sup>+</sup> T cells and natural killer (NK) cells over Tregs but exhibits limited anti-tumor efficacy. We develop a programmed cell death protein 1 (PD-1)-targeted, receptor-masked IL-2 immunocytokine, PD1-IL2Ra-IL2, which attenuates systemic IL-2 activity while maintaining the capacity to engage IL-2Rα on PD-1<sup>+</sup> T cells. Mice treated with PD1-IL2Ra-IL2 s"],"journal":["Cell reports. Medicine"],"pagination":["101747"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11513833"],"repository":["biostudies-literature"],"pubmed_title":["A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies."],"pmcid":["PMC11513833"],"pubmed_authors":["Wu J","Murphy AJ","Crawford A","Davis S","Mohrs K","Krueger P","Wei Y","Macdonald L","Hermann A","Ahmed H","Garg V","DiLillo DJ","Wang Q","Ullman E","Vazzana K","Wang S","Yancopoulos GD","Patel S","Guo C","Ramos W","Bhavsar R","Adler C","Lin JC","Bloch N","Smith E","Yan Y","Ni M","Huang T","Zhang T","Dudgeon D","Antao OQ","Chang AY","Amatulli M","Olson WC"],"additional_accession":[]},"is_claimable":false,"name":"A PD-1-targeted, receptor-masked IL-2 immunocytokine that engages IL-2Rα strengthens T cell-mediated anti-tumor therapies.","description":"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<sup>+</sup> T cells and natural killer (NK) cells over Tregs but exhibits limited anti-tumor efficacy. We develop a programmed cell death protein 1 (PD-1)-targeted, receptor-masked IL-2 immunocytokine, PD1-IL2Ra-IL2, which attenuates systemic IL-2 activity while maintaining the capacity to engage IL-2Rα on PD-1<sup>+</sup> T cells. Mice treated with PD1-IL2Ra-IL2 s","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Oct","modification":"2026-07-15T17:40:40.486Z","creation":"2025-04-04T00:29:15.149Z"},"accession":"S-EPMC11513833","cross_references":{"pubmed":["39326410"],"doi":["10.1016/j.xcrm.2024.101747"]}}