1. Antineoplastic activity of lentiviral vectors expressing interferon-alpha in a preclinical model of primary effusion lymphoma.
- Author
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Calabrò ML, Gasperini P, Di Gangi IM, Indraccolo S, Barbierato M, Amadori A, and Chieco-Bianchi L
- Subjects
- Animals, Cells, Cultured, Cytokines metabolism, Drug Evaluation, Preclinical, Female, Humans, Interferon alpha-2, Kidney cytology, Kidney drug effects, Kidney metabolism, Lymphoma, Primary Effusion genetics, Lymphoma, Primary Effusion pathology, Mesoderm cytology, Mesoderm drug effects, Mesoderm metabolism, Mice, Mice, SCID, Peritoneum cytology, Peritoneum drug effects, Peritoneum metabolism, Recombinant Proteins, Antineoplastic Agents therapeutic use, Genetic Vectors, Interferon-alpha therapeutic use, Lentivirus genetics, Lymphoma, Primary Effusion drug therapy
- 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-alpha(1) (IFN-alpha(1))-expressing lentiviral vector (mIFN-alpha(1)-LV) was compared with that of a human (h) IFN-alpha(2)b-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-alpha(2)b-LV significantly prolonged mice survival and reduced ascites development. Interestingly, mIFN-alpha(1)-LV showed an antineoplastic activity comparable with that observed with hIFN-alpha(2)b-LV. As mIFN-alpha(1) retained species-restricted activity in vitro, it probably acted in vivo on the intracavitary murine milieu. mIFN-alpha(1)-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.
- Published
- 2009
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