Pegylated arginine deiminase (ADI-SS PEG20,000 mw) inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo.

摘要: Some murine melanomas and hepatocellular carcinomas (HCCs) have been shown to be auxotrophic for arginine. Arginine deiminase (ADI; EC 3.5.3.6.), an arginine-degrading enzyme isolated from Mycoplasma, can inhibit growth of these tumors. We found that ADI was specific arginine did not degrade other amino acids. Although is essential acid most cells, all human HCCs tested were inhibited by in vitro. synthesized citrulline two steps argininosuccinate synthetase lyase. Melanomas express mRNA but lyase mRNA, suggesting the auxotrophy cells a result inability produce synthetase. Human transfected with expression plasmid containing cDNA. The much more resistant than parental vitro vivo. Initial attempts use vivo indicated this had little efficacy, consistent its short circulation half-life. Formulation polyethylene glycol ADI-SS PEG(20,000 mw) resulted longer half-life that, although equally effective vitro, efficacious treatment mice implanted HCCs. These data indicate sensitivity melanoma HCC due absence formulation ADI, which causes sustained decrease arginine, may useful tumors including HCC.