Antineoplastic activity of lentiviral vectors expressing interferon-α in a preclinical model of primary effusion lymphoma

Abstract

The peculiar site of development of primary effusion lymphoma (PEL) highlights a specific role of body cavities in the pathogenesis of this neoplasia. We used a xenograft murine model of PEL to characterize the contribution of the host microenvironment to PEL growth. The activity of a murine (ie, host-specific) interferon-α1 (IFN- α1)-expressing lentiviral vector (mIFN-α1-LV) was compared with that of a human (h) IFN-α2b-LV. LVs efficiently delivered the transgene to PEL cells and conferred long-term transgene expression in vitro and in vivo. Treatment of PEL-injected severe combined immunodeficiency mice with hIFN-α2b-LV significantly prolonged mice survival and reduced ascites development. Interestingly, mIFN-α1-LV showed an antineoplastic activity comparable with that observed with hIFN-α2b-LV.As mIFN-α1 retained species-restricted activity in vitro, it probably acted in vivo on the intracavitary murine milieu. mIFN-α1-treated murine mesothelial cells were found to express tumor necrosis factor-related apoptosis-inducing ligand and to significantly trigger apoptosis of cocultured PEL cells in a tumor necrosis factor-related apoptosis-inducing ligand-dependent manner. These data suggest that the interaction between lymphomatous and mesothelial cells lining the body cavities may play a key role in PEL growth control and also indicate that the specific targeting of microenvironment may impair PEL development. © 2009 by The American Society of Hematology.