1. ¹Department of Virology, Hadassah Medical School, The Hebrew University, Jerusalem, Israel
2. ²Department of Hematology, Hadassah Medical Center, The Hebrew University, Jerusalem, Israel

Correspondence: Professor A Panet, Department of Virology, Hadassah Medical School, The Hebrew University, Jerusalem, Israel 91120, Israel. E-mail: amospa@ekmd.huji.ac.il

Received 1 October 2007; Revised 24 February 2008; Accepted 16 April 2008; Published online 6 June 2008.

Abstract

Newcastle disease virus (NDV), an avian paramyxovirus, has a potential oncolytic effect that may be of significance in the treatment of a variety of cancer diseases. An attenuated lentogenic isolate of NDV (HUJ) demonstrated a selective cytopathic effect upon a panel of human and mouse lung tumor cells, as compared to human nontumorigenic lung cells. The virus-selective oncolytic effect is apoptosis dependent, and related to higher levels of viral transcription, translation and progeny virus formation. Furthermore, NDV-HUJ oncolytic activity is directed in-cis and not through induction of cytokines, that may act in-trans on neighboring cells. Development of primary lung tumors and of the consequent metastasis in mice inoculated with mouse lung tumor cells 3LL-D122 was decreased following treatment with NDV-HUJ. The preferential killing of the tumor cells is not due to a deficiency in the interferon (IFN) system, as expression of the IFN- gene, in the infected cells, is properly induced. Moreover, pretreatment with IFN effectively protected the tumor cells from the virus oncolytic effect. We conclude therefore, that NDV-HUJ should have a significant benefit in the treatment of lung cancer as well as other malignancies.