Definition

An engineered, prodrug form of the human endogenous cytokine interleukin-15 (IL-15), composed of a mutated form of IL-15 fused to a Fc fragment and linked to a masking moiety via a tumor protease-cleavable linker, with potential antineoplastic activity. Upon administration of Fc-IL-15 prodrug fusion molecule ASKG315, IL-15 is bound to the masking moiety and pharmacologically inactive. Upon proteolytic cleavage in the tumor microenvironment (TME), active IL-15 is released. IL-15 stimulates the proliferation of natural killer (NK) cells and memory CD8+ T cells. The memory T cells enhance the secretion of the cytokine interferon-gamma (IFN-g), which further potentiates the immune response against tumor cells. This may increase tumor cell killing and decrease tumor cell proliferation. IL-15 regulates CD8+ T- and NK-cell development, activation and proliferation. The selective activation in the TME enhances the IL-15-mediated cytolytic responses against tumor cells while sparing the unwanted effects of systemic, peripheral immune activation.