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Supplementary Fig. S3 from NEI-01-Induced Arginine Deprivation Has Potent Activity Against Acute Myeloid Leukemia Cells Both In Vitro and In Vivo

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posted on 2023-04-03, 18:21 authored by Yijun Cai, Jeremy P.H. Chow, Yu-On Leung, Xiaoxu Lu, Chak-Ho Yuen, Wing Lun Lee, Ka-Chun Chau, Liz L. Yang, Raymond M.H. Wong, Justin Y.T. Lam, Daniel T.L. Chow, Steven H.K. Chung, Sui-Yi Kwok, Yun-chung Leung

ASS1 expression in AML cell lines and normal fibroblast

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New Epsilon Innovation Limited

AML

Hong Kong Polytechnic University

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ARTICLE ABSTRACT

Recent studies have revealed that targeting amino acid metabolic enzymes is a promising strategy in cancer therapy. Acute myeloid leukemia (AML) downregulates the expression of argininosuccinate synthase (ASS1), a recognized rate-limiting enzyme for arginine synthesis, and yet displays a critical dependence on extracellular arginine for survival and proliferation. This dependence on extracellular arginine, also known as arginine auxotrophy, suggests that arginine deprivation would be a treatment strategy for AML. NEI-01, a novel arginine-depleting enzyme, is capable of binding to serum albumin to extend its circulating half-life, leading to a potent anticancer activity. Here we reported the preclinical activity of NEI-01 in arginine auxotrophic AMLs. NEI-01 efficiently depleted arginine both in vitro and in vivo. NEI-01-induced arginine deprivation was cytotoxic to arginine auxotrophic AML cells through induction of cell-cycle arrest and apoptosis. Furthermore, the potent anti-leukemia activities of NEI-01 were observed in three different types of mouse models including human cell line-derived xenograft, mouse cell line-derived homografts in syngeneic mice and patient-derived xenograft. This preclinical data provide strong evidence to support the potential use of NEI-01 as a therapeutic approach in AML treatment.

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    Molecular Cancer Therapeutics

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