A long-acting formulation composed of the human cytokine interleukin-15 (IL-15) that is conjugated by polymers, with potential immunomodulating and anti-tumor activities. Upon administration of polymer-conjugated IL-15 receptor agonist NKTR-255, the IL-15 moiety targets and binds to the alpha subunit of the IL-15 receptor on natural killer (NK) and T-cells, thereby activating the IL-15-mediated pathway. This leads to the expansion and activation of natural killer (NK) cells and memory CD8+ T-cells, thereby enhancing the anti-tumor activity of NKs and long-term memory T-lymphocyte immune responses. This may increase tumor cell killing and decrease tumor cell proliferation. In addition, NKTR-255 may, when combined with a tumor-directed antibody, enhance the antibody-dependent cell-mediated cytotoxicity (ADCC) mechanism. IL-15 is a pro-inflammatory cytokine that plays a key role in the regulation of T- and NK cell activation, proliferation and promotion of their anti-tumor effects. Compared to IL-15 alone, the polymer formulation allows for increased retention at the tumor site and reduced clearance, thereby increasing the effect of IL-15.