pegargiminase + cisplatin

Pegargiminase + cisplatin is a combination therapy of **pegargiminase** (ADI-PEG20, a pegylated enzyme that depletes arginine) with the chemotherapy agent **cisplatin**. Pegargiminase is a recombinant arginine deiminase enzyme produced in genetically modified bacteria and pegylated to prolong half-life. It catalyzes the degradation of arginine to citrulline and ammonia, targeting tumors (such as nonepithelioid mesothelioma and ASS1-deficient uveal melanoma) that are unable to synthesize arginine due to loss of function of argininosuccinate synthetase 1 (ASS1). By depleting arginine, the combination exploits the metabolic vulnerability of these cancers, increasing their sensitivity to cisplatin and enhancing cytotoxicity. Cisplatin is a platinum-based chemotherapeutic that induces crosslinking of DNA, leading to apoptosis. Pegargiminase + cisplatin (often combined as a triplet with pemetrexed) has shown survival benefit and manageable toxicity in phase 1 through 3 clinical trials for ASS1-deficient mesothelioma and uveal melanoma.[1][2][3][5]

Other names

pegylated arginine deiminase + cisplatin