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- W2890274375 abstract "Significance Regulatory T cells (Tregs) infiltrate tumors in various cancers and promote an immunosuppressive microenvironment that hinders antitumor immunity. Denileukin diftitox, a diphtheria-toxin–based fusion protein that depletes Tregs, was approved for the treatment of T cell malignancies, but its clinical use was limited due to the presence of protein aggregates and toxicity associated with vascular leakage. Here, we report the production of a second-generation IL-2 receptor-targeted, fully-folded, monomeric diphtheria fusion toxin and a V6A mutant variant that showed reduced vascular leak in vitro and reduced lethality in mice. In a mouse model of melanoma, we found a significant decrease in tumor growth associated with reduction in Tregs when the protein was tested as monotherapy or in combination with checkpoint blockade." @default.
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- W2890274375 date "2019-02-04" @default.
- W2890274375 modified "2023-10-12" @default.
- W2890274375 title "Second-generation IL-2 receptor-targeted diphtheria fusion toxin exhibits antitumor activity and synergy with anti–PD-1 in melanoma" @default.
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- W2890274375 doi "https://doi.org/10.1073/pnas.1815087116" @default.
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