The VE-PTP Inhibitor AKB-9778 Improves Antitumor Activity and Diminishes the Toxicity of Interleukin 2 (IL-2) Administration.

ABSTRACT: Administration of interleukin (IL)-2 has led to a durable response in patients with advanced renal cancer and melanoma but is restricted for clinical application because of adverse effects, including the vascular leak syndrome (VLS). VLS is associated with increased circulating levels of the Tie2 antagonist ligand, angiopoietin 2, and decreased Tie2 receptor phosphorylation and downstream signaling in endothelial cells (ECs). Given that vascular endothelial protein tyrosine phosphatase (VE-PTP) is a specific membrane phosphatase in ECs that dephosphorylates Tie2, the effects of targeting VE-PTP by a selective inhibitor AKB-9778 (AKB) in terms of VLS and antitumor efficacy were examined in this study. The authors found, by targeting VE-PTP, that the antitumor effects induced by IL-2 were au

SUBMITTER: Li G 

PROVIDER: S-EPMC8088541 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature