title: Antineoplastic activity of lentiviral vectors expressing interferon-alpha 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-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.
authors.affiliation: Immunology and Diagnostic Molecular Oncology, Istituto Oncologico Veneto, Istituto di Ricovero e Cura a Carattere Scientifico, Padova, Italy. lcalabro@unipd.it
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Calabrò
authors.forename: Paola
authors.initials: P
authors.lastname: Gasperini
authors.forename: Iole Maria
authors.initials: IM
authors.lastname: Di Gangi
authors.forename: Stefano
authors.initials: S
authors.lastname: Indraccolo
authors.forename: Massimo
authors.initials: M
authors.lastname: Barbierato
authors.forename: Alberto
authors.initials: A
authors.lastname: Amadori
authors.forename: Luigi
authors.initials: L
authors.lastname: Chieco-Bianchi
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D005260:Female; D005822:Genetic Vectors; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016086:Lentivirus / Q000235:genetics*; D054685:Lymphoma, Primary Effusion / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008648:Mesoderm / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016513:Mice, SCID; D010537:Peritoneum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: D000970:Antineoplastic Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins