Principal Investigators: Prof. Thomas Leung and Dr. Thomas Lo

Further to our pervious success, we have designed another potential anti-cancer agent based on the naturally occurring enzyme, arginase, originating from an extreme thermophilic bacterium. Using the state-of-the-art DNA technology and site specific pegylated technologies we have rationally designed and synthesized BCA-PEG20, an effective, safe, highly stable drug with potent anti-cancer activities.

The main constituent of BCA-PEG20 is arginase, an enzyme that degrades arginine. Arginine is necessary for cell growth; it can be produced by normal cells in the human body. However, restriction of arginine inhibits growth of cancer cells, because these cancer cells are unable to produce arginine so they extract it instead from the blood. Depleting arginine in the blood thus starves cancer cells to death while normal cells are unaffected.

BCA-PEG20 has potent anti-cancer activities on a variety of cancers, including lung cancer, colorectal cancer, liver cancer, breast cancer, gastric and esophageal cancers. Our drug also shows synergy with chemo drugs to enhance therapeutic effects. This invention has awarded the Prize of the State of Geneva and a Gold Medal with Jury’s Commendation in the 37th International Exhibition of Invention, New Techniques and Products in Geneva in 2009. Patent in US and other counties have been filed. BCA-PEG20 is currently undergoing pre-clinical studies.

Related Publications:

1. Cheng, P.N.; Leung, Y.C.; Lo, W.H.; Tsui, S.M. and Lam, K.C. Remission of hepatocellular carcinoma with arginine depletion induced by systemic release of endogenous hepatic arginase due to transhepatic arterial embolisation, augmented by high-dose insulin: arginase as a potential drug candidate for hepatocellular carcinoma. Cancer Letters (2005), 224:67-80
2. Cheng, P.N.M.; Lam, T.L.; Lam, W.M.; Tsui, S.M.; Cheng, A.W.M.; Lo, W.H. and Leung, Y.C. Pegylated human recombinant arginase (hrArg-peg5,000mw) inhibits the in vitro and in vivo proliferation of human hepatocellular carcinoma through arginine depletion; Relationship to urea cycle enzymes, especially ornithine transcarbamylase. Cancer Research, 67, 309-317 (2007), 67(1):309-17
3. Lam, T.L.; Wong, G. K. ; Chong, H.C.; Cheng, P.N.; Choi, S.C.; Chow, T.L.; Kwok, S.Y.; Poon, R.T.; Wheatley, D.N.; Lo, W.H. and Leung, Y.C. Recombinant human arginase inhibits proliferation of human hepatocellular carcinoma by inducing cell cycle arrest. Cancer Lett (2009), 277(1):91-100
4. Tsui, S.M.; Lam, W.M.; Lam, T.L.; Chong, H.C.; So, P.K.; Kwok, S.Y.; Arnold, S.; Cheng, P.N.M.; Wheatley, D.N.; Lo, W.H. and Leung, Y.C. Pegylated derivatives of recombinant human arginase (rhArg1) for sustained in vivo activity in cancer therapy: preparation, haracterization and analysis of their pharmacodynamics in vivo and in vitro and action upon hepatocellular carcinoma cell (HCC). Cancer Cell International (2009), 17;9:9
5. Lam TL, Wong GK, Chow HY, Chong HC, Chow TL, Kwok SY, Cheng PN, Wheatley DN, Lo WH, Leung YC., Recombinant human arginase inhibits the in vitro and in vivo proliferation of human melanoma by inducing cell cycle arrest and apoptosis. Pigment Cell Melanoma Res (2011), 24(2):366-76
6. Yau T, Cheng PN, Chan P, Chan W, Chen L, Yuen J, Pang R, Fan ST, Poon RT. A phase 1 dose-escalating study of pegylated recombinant human arginase 1 (Peg-rhArg1) in patients with advanced hepatocellular carcinoma. Invest New Drugs. 2013 Feb;31(1):99-107