Endogenous arginase 2 as a potential biomarker for PEGylated arginase 1 treatment in xenograft models of squamous cell lung carcinoma.

摘要: Depletion of arginine induced by PEGylated arginase 1 (ARG1) (BCT-100) has shown anticancer effects in auxotrophic cancers that lack argininosuccinate synthetase (ASS1) and ornithine transcarbamylase (OTC). High levels endogenous 2 (ARG2) have been previously reported human lung cancers. Although a high-ARG2 level neither causes immunosuppression nor affects disease progression, it may theoretically affect the efficacy ARG1 treatment. ARG2 was to be highly expressed H520 squamous cell carcinoma (lung SCC) xenografts but undetectable SK-MES-1 SW900 SCC xenografts. We propose high-endogenous expression could impede anti-tumor effect SCC. The vivo investigated using three xenograft models (60 mg/kg) suppressed tumor growth not ASS1 while OTC remained low all A detected only Serum decreased significantly Nonetheless intratumoral SW900, In xenografts, treatment G1 arrest, downregulation Ki67 Mcl-1 activation apoptosis. upregulation Bim apoptosis were observed upon Silencing re-sensitized treatment, partially mediated through depletion via arrest effective with low-endogenous ASS1/OTC ARG2. High-endogenous cause resistance serve as third predictive biomarker