ArticleACS central science2026
A Tumor-Microenvironment-Responsive Chemically Masked IL‑2 Prodrug Potentiates PD‑1 Checkpoint Blockade and Elicits Robust Antitumor Efficacy.
Article in ACS central science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Authors and funding
13 authors.
Funding
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Abstract
Interleukin-2 (IL-2) is a potent mediator of T-cell activation with significant potential for cancer immunotherapy, yet its clinical utility is severely constrained by its narrow therapeutic window. Here we report a chemically masked IL-2 prodrug (Cm-proIL2) that enables tumor-microenvironment-responsive cytokine activation through tumor-associated protease cleavage. Site-specific conjugation of a poly-(ethylene glycol) (PEG) moiety selectively masks peripheral receptor engagement, while PEG removal within the tumor microenvironment restores IL-2 receptor binding and reduces molecular size, thereby enhancing intratumoral lymphocyte penetration and effector T cell functionality. Building on this modular platform, we further engineered a PD-1-targeted nanobody fusion, PD1-Cm-proIL2, to enable the cis delivery of IL-2 activity to PD-1
Identifiers
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.