Oncolytic therapy of a recombinant Newcastle disease virus D90 strain for lung cancer
ABSTRACT
BACKGROUND: Lung cancer is one of the leading causes of deaths from cancer worldwide. Tumor virotherapy using naturally oncolytic Newcastle disease virus (NDV) has been shown to be safe and effective in preclinical studies and clinical trials. Previously, we have reported the NDV D90 strain that was isolated from natural source has an antiproliferative effect in human lung cancer cell line A549.
METHODS AND RESULTS: In this study, we constructed a reverse genetics system based on the oncolytic NDV D90 strain and generated a recombinant NDV carrying a gene encoding enhanced green fluorescent protein (rNDV-GFP). The rescued virus rNDV-D90 and rNDV-GFP showed the similar characteristics of replication and apoptotic ability in lung cancer A549 cells, which suggested that the recombinant viruses sustained the property of tumor-selective replication and induced apoptosis of tumor cells. The athymic mice bearing implanted lung cancer were treated with the parental D90 virus, the rescued rNDV-D90 and rNDV-GFP via intratumoral injections, respectively. The results showed that the recombinant viruses as well as the parental D90 virus significantly suppressed the loss of body weight and tumor growth.
CONCLUSIONS: The study provides a new platform to develop effective therapeutic agents for tumor treatment. The availability of the reverse genetics system for NDV D90 strain will make it possible to develop novel recombinant oncolytic viruses based on the NDV D90 strain for improving the efficacy of tumor treatment.