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.

Unlocking the Potential of Arginine Deprivation Therapy: Recent Breakthroughs and Promising Future for Cancer Treatment

“…NEI-01 is another novel ADI-based drug that selectively depletes arginine in tumor cells to induce metabolic stress and cell death. NEI-01 has greater specificity for cancer cells and a longer half-life due to its albumin-binding domain [ 90 ]. In preclinical studies, NEI-01 showed potent anticancer activity against different types of cancer, including pancreatic cancer and leukemia [ 90 , 91 ].…”

“…NEI-01 has greater specificity for cancer cells and a longer half-life due to its albumin-binding domain [ 90 ]. In preclinical studies, NEI-01 showed potent anticancer activity against different types of cancer, including pancreatic cancer and leukemia [ 90 , 91 ]. NEI-01 treatment significantly reduced tumor volume and weight in a human pancreatic mouse xenograft model and demonstrated potent anti-leukemia activities in three different types of mouse models [ 90 , 91 ].…”

“…In preclinical studies, NEI-01 showed potent anticancer activity against different types of cancer, including pancreatic cancer and leukemia [ 90 , 91 ]. NEI-01 treatment significantly reduced tumor volume and weight in a human pancreatic mouse xenograft model and demonstrated potent anti-leukemia activities in three different types of mouse models [ 90 , 91 ]. Currently, a phase I clinical trial (NCT05226468) of NEI-01 in patients with advanced solid tumors and lymphoma is ongoing, which may represent a potential new approach to arginine deprivation therapy for cancer treatment.…”

When AIE meets enzymes

“…It is essential in various cellular events such as gene expression, metabolic pathways, cell growth and differentiation, and signaling. 1–3 Most of the complex biochemical processes in the body are regulated by one or more enzymes. Abnormal manifestations of enzyme activities will indicate the health status of the body and can be used as a biomarker for diagnosing diseases.…”