Since ISG15 has been reported to mediate both pro-inflammatory and immunoregulatory activities as an extracellular, cytokine-like molecule (20, 24–28), we further investigated whether the therapeutic efficacy of ADU-S100 could be improved by coadministration of blocking/neutralizing anti-ISG15 antibody in the B16 and BPR20 melanoma models (Figure 5A). The gene discussed is ISG15; the disease is melanoma.