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

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.
Competing Interests: All the authors (JPHC, YC, DTLC, SHKC, KCC, KYN, OML, RMHW, AWLL, YOL, SYK), except YCL, are employees of New Epsilon Innovation Limited. There are no related patents, products in development, or marketed products to declare. This does not alter the authors’ adherence to all PLOS ONE policies on sharing data and materials.