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

摘要

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 micro-environment to PEL growth. The activity of a murine (ie, host-specific) interferon-a (IFN--expressing lentiviral vector (mlFN--LV) was compared with that of a human (h) IFN-b-LV. LVs efficiently delivered the transgene to PEL cells and conferred long-term transgene expres-sion in vitro and in vivo. Treatment of PEL-injected severe combined immunodeficiency mice with hlFN-b-LV significantly prolonged mice survival and reduced ascites development. Interestingly, mlFN-LV showed an antineoplastic activity comparable with that observed with hlFN-b-LV. As mlFN- retained species-restricted activity in vitro, it probably acted in vivo on the intracavitary murine milieu. mlFN--treated murine mesothe-lial cells were found to express tumor necrosis factor-related apoptosis-induc-ing ligand and to significantly trigger apo-ptosis of cocultured PEL cells in a tumor necrosis factor-related apoptosis-induc-ing ligand-dependent manner. These data suggest that the interaction between lym-phomatous and mesothelial cells lining the body cavities may play a key role in PEL growth control and also indicate that the specific targeting of microenviron-ment may impair PEL development.