Pegylated arginine deiminase: a novel anticancer enzyme agent

Abstract

Pegylated arginine deiminase (ADI-PEG20) is a novel anticancer enzyme that produces depletion of arginine, which is a nonessential amino acid in humans. Certain tumours, such as malignant melanoma and hepatocellular carcinoma, are auxotrophic for arginine. These tumours that are sensitive to arginine depletion do not express argininosuccinate synthetase, a key enzyme in the synthesis of arginine from citrulline. ADI-PEG20 inhibits human melanomas and hepatocellular carcinomas in vitro and in vivo. Phase I -II trials in patients with melanoma and hepatocellular carcinomas have shown the drug to have antitumour activity and tolerable side effects. Large Phase II trials and randomised, controlled Phase III trials are needed to determine its overall efficacy in the treatment of these malignancies and others.

Pegylated Recombinant Human Arginase (rhArg-peg5,000mw) Inhibits the In vitro and In vivo Proliferation of Human Hepatocellular Carcinoma through Arginine Depletion

“…Tumors (mainly malignant melanoma and HCC) that are sensitive to arginine depletion by ADI do not express ASS (4,12,13). Shen et al (14) reported that many cell lines are resistant to ADI treatment, although most require arginine for proliferation.…”

Arginine enzymatic deprivation and diet restriction for cancer treatment

“…As the bacterial enzyme is highly immunogenic in humans, therapeutic preparations of ADI have been conjugated with polyethylene glycol (20 000 Da; ADI-PEG20) that serves to reduce the immunogenicity of the enzyme while greatly improving its pharmacokinetic halflife in serum (Feun, Savaraj, 2006;Feun et al, 2008;Ni, Schwaneberg, Sun, 2008).…”

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“…ADI-PEG20 treatment causes Arg starvation resulting in tumor cell death of autophagy/ apoptosis. ADI-PEG20 has been in clinical investigations for treating ASS1 low tumors with promising results [2]. One major problem associated with ADI-PEG20 treatment is drug resistance due mostly to induction of ASS1 expression.…”