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

  • PLoS One. 2020 Apr 30;15(4):e0231633. doi: 10.1371/journal.pone.0231633.
Jeremy P H Chow  1 ,  Yijun Cai  1 ,  Daniel T L Chow  1 ,  Steven H K Chung  1 ,  Ka-Chun Chau  1 ,  Ka-Ying Ng  1 ,  Oscar M Leung  1 ,  Raymond M H Wong  1 ,  Alan W L Law  1 ,  Yu-On Leung  1 ,  Sui-Yi Kwok  1 ,  Yun-Chung Leung  2
Affiliations
  • 1. New Epsilon Innovation Limited, Hong Kong, China.
  • 2. 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.
PMID: 32353864 DOI: 10.1371/journal.pone.0231633
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.

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