IL-15 receptor pathway (NK cells / memory CD8+ T cells)

Class

Fusion protein — IL-15/IL-15Rα complex fused to a bispecific Fc domain (immunocytokine); stimulates proliferation of NK cells and memory CD8+ T cells, enhancing IFN-γ secretion and anti-tumor immune response

Pathway

IL-15/IL-15Rα cytokine signaling

The IL-15 receptor pathway governs the survival, proliferation, and effector function of natural killer (NK) cells and memory CD8+ T cells, two lymphocyte populations central to immune surveillance against tumors and infected cells. IL-15 is a cytokine that, unlike its relative IL-2, is typically presented to responding cells bound to a partner protein called IL-15Rα rather than circulating freely — a process known as trans-presentation. Engaging this pathway drives lymphocyte expansion and boosts secretion of interferon-gamma (IFN-γ), a signaling protein that coordinates broader immune activation, alongside increased cytotoxic capacity against abnormal cells. Because IL-15 preferentially expands NK cells and memory CD8+ T cells rather than immunosuppressive regulatory T cells, it is considered an attractive lever for cancer immunotherapy, where the goal is to amplify tumor-killing lymphocytes without simultaneously strengthening the suppressive arm of the immune system. The engineered format described here — an IL-15/IL-15Rα complex fused to an antibody Fc domain — recreates the natural trans-presentation architecture while extending the molecule's persistence in circulation, addressing the very short natural half-life of free IL-15. This mechanism is broadly relevant across solid and hematologic cancers where enhancing innate and memory immune responses may improve tumor control, often alongside other immune-directed therapies.