engineered IL-2 prodrug WTX-124

An engineered, prodrug form of the human endogenous cytokine interleukin-2 (IL-2), composed of IL-2 linked to an inactivation domain via a tumor protease-sensitive linker, and a half-life extension domain, with potential immunoregulatory and antineoplastic activities. Upon administration of engineered IL-2 prodrug WTX-124, IL-2 is bound to the inactivation domain and pharmacologically inactive. Upon proteolytic cleavage in the tumor microenvironment (TME), active IL-2 is released. IL-2 binds to the high-affinity IL-2 receptors expressed on CD8+ T cells and natural killer (NK) cells, thereby activating IL2R-mediated signaling. The activation and expansion of CD8+ T cells and NK cells mediate cytolytic immune responses against tumor cells, which kills tumor cells and inhibits tumor cell proliferation. The selective activation in the TME enhances the IL-2-mediated cytolytic responses against tumor cells while sparing the unwanted effects of systemic, peripheral immune activation. The inclusion of the half-life extension domain prolongs the agent's exposure in the tumor.