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A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells.

ABSTRACT: Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetectable level for at least 9 days. Treatment of NEI-01 specifically inhibited cell viability of MIA PaCa-2 and PANC-1 cancer cell lines, which were ASS1 negative. Using a human pancreatic mouse xenograft model, NEI-01 treatment significantly reduced tumor volume and weight. Our data provides proof of principle for a cancer treatment strategy using NEI-01.

SUBMITTER: Chow JPH

PROVIDER: S-EPMC7192632 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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A modified arginine-depleting enzyme NEI-01 inhibits growth of pancreatic cancer cells.

Chow Jeremy P H JPH Cai Yijun Y Chow Daniel T L DTL Chung Steven H K SHK Chau Ka-Chun KC Ng Ka-Ying KY Leung Oscar M OM Wong Raymond M H RMH Law Alan W L AWL Leung Yu-On YO Kwok Sui-Yi SY Leung Yun-Chung YC

PloS one 20200430 4

Arginine deprivation cancer therapy targets certain types of malignancies with positive result in many studies and clinical trials. NEI-01 was designed as a novel arginine-depleting enzyme comprising an albumin binding domain capable of binding to human serum albumin to lengthen its half-life. In the present work, NEI-01 is shown to bind to serum albumin from various species, including mice, rat and human. Single intraperitoneal administration of NEI-01 to mice reduced plasma arginine to undetec ...[more]

PMID: 32353864

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