Selective oncolytic effect of an attenuated Newcastle disease virus (NDV-HUJ) in lung tumors.
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-beta 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.
Department of Virology, Hadassah Medical School, The Hebrew University, Jerusalem, Israel.
B
B
Yaacov
E
E
Eliahoo
E
E
Elihaoo
I
I
Lazar
M
M
Ben-Shlomo
I
I
Greenbaum
A
A
Panet
Z
Z
Zakay-Rones
D000818:Animals; D017209:Apoptosis; D006801:Humans; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D023421:Models, Animal; D009522:Newcastle disease virus / Q000235:genetics / Q000378:metabolism*; D050130:Oncolytic Virotherapy; D050504:Oncolytic Viruses / Q000235:genetics / Q000378:metabolism*; D014779:Virus Replication
D016899:Interferon-beta