xCT, the Na+-independent cystine/glutamate antiporter, which is encoded by the SLC7A11 gene represents an important therapeutic oncology target and is the focus of AgilVax’s antibody-based development pipeline. xCT mediates the exportation of intracellular glutamate and the importation of extracellular cystine. The cystine is converted to cysteine, which is required for glutathione (GSH) synthesis. GSH is important for protection of the cell against oxidative stress and chemical insults.
Cancer cells contain high concentrations of GSH for mitigating reactive oxygen species generation and detoxification. High GSH levels buffer oxidative stress in cancer cells that would otherwise cause cell death. Extracellular cystine is readily abundant (approximately 50 μM) within the body, as the liver produces and exports a great amount of cysteine that is quickly oxidized. This surplus of cystine is utilized by cancer cells to elevate intracellular cysteine levels for catabolic usage. As a consequence of their dependency on xCT to acquire cysteine, cancer cells become vulnerable to modulation of xCT activity and metabolic processes related to xCT.
xCT expression is restricted in normal cell but has been reported to be elevated in breast, colorectal, lung, hepatocellular, and pancreatic cancers and has been linked to with poor patient survival. Thus, xCT possesses all the features of an ideal target for antibody-based therapies against undifferentiated and more differentiated cancer cells.