Arginine depletion potentiates standard-of-care chemo-immunotherapy in preclinical models of high-risk neuroblastoma.

ABSTRACT:

Background

Dysregulated amino acid metabolism creates cancer-specific vulnerabilities. Neuroblastoma tumors have dysregulated arginine metabolism that renders them sensitive to systemic arginine deprivation. Arginase therapy has been proposed as a therapeutic approach for neuroblastoma treatment and has a favorable safety profile in pediatric cancer patients, however optimal therapeutic combinations remain unexplored.

Methods

The anti-tumor effects of BCT-100, a pegylated human arginase, were studied in neuroblastoma cell models by metabolite profiling, proteomics, and viability, clonogenicity, and protein translation assays. BCT-100 efficacy was assessed in the Th-MYCN transgenic neuroblastoma mouse model and in neuroblastoma cell line and patient-derived xenograft models.<

SUBMITTER: Hanssen KM 

PROVIDER: S-EPMC12351974 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature