Rational Design of Engineered Arginine Depleting Enzymes as Multi-potent Anti-cancer Agents

Arginine deprivation has become a new cancer treatment paradigm and has exploited for treatment of various cancers. Arginine is an essential amino acid for the growth of cancer cells. Deprivation of arginine induces cancer cells death but it is generally well tolerated in normal cells. The successful use of Arginine Deiminase (ADI) to treat argininosuccinate synthetase (ASS)-deficient tumors has opened up new possibilities for targeted therapy. Nevertheless, many ASS-positive cancers are resistance to ADI.

By rational drug design, we have developed a thermostable arginase (BCA-PEG20) to treat both ADI-sensitive and ADI-resistant cancers. BCA-PEG20 has demonstrated to have antitumor activities both in vitro and in vivo in lung cancer, liver cancer, colorectal cancer, gastric cancer, cervical cancer and other tumors. As a novel multipotent anti-cancer drug, BCA-PEG20 is able to work as a single agent and combine with other chemotherapeutic agents to enhance treatment effect.