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

Autor:	Cai Y; New Epsilon Innovation Limited, Hong Kong, China. thomas.yun-chung.leung@polyu.edu.hk thea.cai@newbetainnovation.com christine.kwok@newbetainnovation.com., Chow JPH; New Epsilon Innovation Limited, Hong Kong, China., Leung YO; New Epsilon Innovation Limited, Hong Kong, China., Lu X; New Epsilon Innovation Limited, Hong Kong, China., Yuen CH; New Epsilon Innovation Limited, Hong Kong, China., Lee WL; New Epsilon Innovation Limited, Hong Kong, China., Chau KC; New Epsilon Innovation Limited, Hong Kong, China., Yang LL; New Epsilon Innovation Limited, Hong Kong, China., Wong RMH; New Epsilon Innovation Limited, Hong Kong, China., Lam JYT; New Epsilon Innovation Limited, Hong Kong, China., Chow DTL; New Epsilon Innovation Limited, Hong Kong, China., Chung SHK; New Epsilon Innovation Limited, Hong Kong, China., Kwok SY; New Epsilon Innovation Limited, Hong Kong, China. thomas.yun-chung.leung@polyu.edu.hk thea.cai@newbetainnovation.com christine.kwok@newbetainnovation.com., Leung YC; State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology and Lo Ka Chung Research Centre for Natural Anti-Cancer Drug Development, The Hong Kong Polytechnic University, Hong Kong, China. thomas.yun-chung.leung@polyu.edu.hk thea.cai@newbetainnovation.com christine.kwok@newbetainnovation.com.
Jazyk:	angličtina
Zdroj:	Molecular cancer therapeutics [Mol Cancer Ther] 2021 Nov; Vol. 20 (11), pp. 2218-2227. Date of Electronic Publication: 2021 Aug 25.
DOI:	10.1158/1535-7163.MCT-21-0120
Abstrakt:	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. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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