Treatment of Malignant Melanoma by Downregulation of XIAP and Overexpression of TRAIL with a Conditionally Replicating Oncolytic Adenovirus

Background and Aim: Currently available systemic therapies for malignant melanoma produce low responserates in patients, and more effective treatment modalities are clearly needed. The tumor necrosis factor (TNF)-related apoptosis-inducing ligand has a significant impact on therapy for patients with X-linked inhibitor ofapoptosis protein-downregulation malignant melanoma. The primary objective of this study was to assess itstherapeutic potential. Materials and
Methods: We employed a conditionally replicating oncolytic adenoviralvector, named CRAd5.TRAIL/siXIAP, with the characteristics of over-expression of the therapeutic gene TRAILand downregulation of XIAP in one vector. B16F10-luc cells were employed to detect anti-tumor activity ofCRAd5.TRAIL/siXIAP in vitro and in vivo.
Results: CRAd5.TRAIL/siXIAP enhanced caspase-8 activation andcaspase-3 maturation in B16F10 cells in vitro. Furthermore, it more effectively infected and killed melanomacells in vitro and in vivo than other adenoviruses.
Conclusion: Taken together, the combination of upregulationof TRAIL and downregulation of siXIAP with one oncolytic adenoviral vector holds promise for developmentof an effective therapy for melanomas and other common cancers.