Optimized expression of human interleukin-15 in Nicotiana benthamiana and in vitro assessment of its activity on human keratinocytes

Human interleukin-15 (hIL-15) is a cytokine essential for immune modulation with therapeutic applications in cancer and chronic wound healing. Although hIL-15 is commercially available, large-scale production studies remain limited. With promising clinical trial results, demand for hIL-15 is expected to rise. Plant expression systems offer a sustainable, low-cost alternative for rapid biopharmaceutical production. In this study, we optimized hIL-15 expression in <i>Nicotiana benthamiana</i> and assessed its physicochemical properties and biological activity. We fused hIL-15 to the Fc domain of human IgG1 for efficient purification. Through optimization of the pre- and post-infiltration conditions, we achieved transient expression and recovery at 4 dpi, yielding 33.8 µg/g fresh weight. Peptide mapping confirmed 97 % overall sequence coverage of the primary structure. Treatment with plant-produced hIL-15-Fc effectively promoted human keratinocyte HaCaT cell proliferation and migration <i>in vitro</i>. These findings demonstrated the potential of plant-based platforms for producing therapeutic recombinant hIL-15 that support wound healing.