NEI-01-induced arginine deprivation has potent activity against acute myeloid leukemia cells both in vitro and in vivo

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

Research output: Journal article publicationJournal articleAcademic researchpeer-review

2 Citations (Scopus)

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 antileukemia 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.

Original languageEnglish
Pages (from-to)2218-2227
Number of pages10
JournalMolecular Cancer Therapeutics
Volume20
Issue number11
DOIs
Publication statusPublished - 1 Nov 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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