Recombinant Newcastle disease virus (rNDV) have shown oncolytic therapeutic efficacy in preclinical studies and are currently in clinical trials. In this study, we have evaluated the possibility to enhance the cancer therapeutic potential of NDV by means of inserting both interleukin-2 (IL-2) and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) delivered by rNDV. We demonstrated that rNDV expressing TRAIL (rNDV-TRAIL) or both human IL-2 and TRAIL (rNDV-IL-2-TRAIL) significantly enhanced inherent anti-neoplastic of rNDV by inducing apoptosis. And we showed that apoptosis-related genes mRNA expression was increased after treated with rNDV-TRAIL or rNDV-IL-2-TRAIL compared with rNDV and rNDV-IL-2. We also demonstrated that both rNDV-IL-2 and rNDV-IL-2-TRAIL induced proliferation of the CD4+ and CD8+ in treated mice and elicited expression of TNF-α and IFN-γ antitumor cytokines. These mice treated with oncolytic agents exhibited significant reduction in tumor development compared with mice trea...

Recombinant Newcastle disease virus (rNDV) as antitumor agent has been shown to be effective for cancer therapy. And TNF-related apoptosis-inducing ligand (TRAIL) also has been demonstrated potentially cancer-therapeutic effects. In this study, we constructed TRAIL delivered by rNDV (rNDV-TRAIL) and investigated whether TRAIL would generate the potential synergistic therapeutic effects with rNDV for cancer therapy. In vitro experiments indicated that TRAIL expressed by rNDV demonstrated good biological activity. TRAIL significantly enhanced inducing apoptosis of rNDV in death receptor expression cancer cell lines. Experiments in malignant melanoma-bearing mice demonstrated that expression of TRAIL delivered by rNDV significantly inhibited the tumor growth and prolonged the survival of treated animals compared to control. In conclusion, oncolytic capacity of rNDV was augmented by TRAIL and the inherent anti-neoplastic properties of NDV were enhanced by the introduction of therapeutic TRAIL gene.