Construction of Recombinant Newcastle Disease Virus Italien Strain for Oncolytic Virotherapy of Tumors

Abstract

Newcastle disease virus (NDV) is a naturally oncolytic virus that has been shown to be safe and effective for cancer therapy. Tumor virotherapy using NDV emerged in the 1950s and has advanced more recently by the increased availability of reverse genetics technology. In this study, we constructed a reverse genetics system based on the virulent and oncolytic NDV Italien strain, and generated two recombinant NDVs carrying a gene encoding either enhanced green fluorescent protein or firefly luciferase. We evaluated the replication and antitumor characteristics of these viruses in vitro and in vivo. Our data showed that the insertion of exogenous reporter genes did not affect NDV replication and sensitivity to type I interferon. The recombinant NDVs kept the property of tumor-selective replication both in vitro and in vivo and strongly induced syncytium formation leading to cell death. Moreover, the recombinant NDVs significantly prolonged the survival of tumor-bearing athymic mice (p=0.017) and suppressed the loss of body weight after intratumoral injection. Taken together, our study provides a novel platform to develop recombinant oncolytic viruses based on the NDV Italien strain and shows the efficiency of recombinant NDV Italien for oncolytic virotherapy of tumors. Wei and colleagues evaluate the replication and antitumor characteristics of two recombinant Newcastle disease viruses (NDVs) based on the virulent and oncolytic Italien strain of NDV. The recombinant NDVs exhibit tumor-selective replication both in vitro and in vivo, strongly inducing syncytium formation leading to cell death as well as significantly prolonging the survival of tumor-bearing athymic mice after intratumoral injection.