Furthermore, to attenuate IL-15-induced off-target toxicity, a next-generation tumor-conditional IL-15, called pro-IL15, was developed to fulfill tumor-targeted delivery by fusing the extracellular domain of IL-15Rβ into the N-terminus of IL-15-IL-15Rα-Fc (super IL-15-Fc) using a peptide linker specifically cleaved by matrix metalloproteinase (MMP) inside the TME [123]. The gene discussed is IL2RB; the disease is neoplasm.