PEGylated arginine deiminase can modulate tumor immune microenvironment by affecting immune checkpoint expression, decreasing regulatory T cell accumulation and inducing tumor T cell infiltration.

PEGylated arginine deiminase (ADI-PEG 20) is being investigated in clinical studies in arginine auxotrophic cancers and is well-tolerated. The anti-tumor properties of ADI-PEG 20 have been extensively investigated - ADI-PEG 20 inhibits the growth of auxotrophic cancers and - however, its impact on immune cells is largely unknown. Here we report the potential impact of ADI-PEG 20 on the tumor immune microenvironment.

Down-regulation of argininosuccinate synthetase is associated with cisplatin resistance in hepatocellular carcinoma cell lines: implications for PEGylated arginine deiminase combination therapy.

Background: Many advanced human tumors, including hepatocellular carcinomas (HCC) are auxotrophic for arginine due to down-regulation of argininosuccinate synthetase (ASS1), the rate-limiting enzyme in arginine synthesis. The arginine-lowering agent PEGylated arginine deiminase (ADI-PEG 20) has shown efficacy as a monotherapy in clinical trials for treating arginine-auxotrophic tumors and is currently being evaluated in combination with cisplatin in other cancer types. Epigenetic silencing via methylation of the ASS1 promoter has been previously demonstrated in other cancer types, and a reciprocal relationship between ASS1 expression and cisplatin resistance has also been observed in ovarian cancer.