Cancer cells need a continuous supply of nutrients to maintain their abnormal growth and rapid division. Not only glucose, but also amino acids are essential to support the high metabolic demands of tumor cells.
The first cancer metabolism targeting product candidate developed in house is eryaspase, consisting of the enzyme L-asparaginase encapsulated inside red blood cells. L-asparaginase breaks down asparagine, a naturally occurring amino acid, into aspartic acid and ammonia. All cells need asparagine for their protein synthesis and growth. Normal cells will obtain the majority of its asparagine needs through its own synthesis. Cancer cells also need asparagine to grow and proliferate, even more than normal cells, but most cancer cells cannot produce enough asparagine. They must rely on circulating asparagine in order to survive. L-asparaginase removes circulating asparagine, thereby depriving cancer cells of a key nutrient and causing them to die. The use of L-asparaginase is a well-established treatment in pediatric acute lymphoblastic leukemia (ALL) treatment, but toxicity has limited its use beyond this patient population. With eryaspase, we aim to broaden the scope of L-asparginase beyond pediatric ALL with focus on selected solid tumors such as pancreatic cancer and triple-negative breast cancer.
Other amino acids such as arginine and methionine have been shown to be involved in a number of biosynthetic pathways that significantly influence carcinogenesis and tumor biology. We are evaluating the encapsulation of methionine-g-lyase and arginine deiminase to induce tumor starvation by targeting these amino acids.