Nuova ricerca

IVANA LAGRECA

COLLABORATORE COORDINATO CONTINUATIVO
Dipartimento di Scienze Mediche e Chirurgiche Materno-Infantili e dell'Adulto

Home |


Pubblicazioni

2023 - Characteristics and clinical behavior of acute myeloid leukemia harboring rare non-A/B/D nucleophosmin (NPM1) gene mutation subtypes: a single-center experience and review of the literature [Articolo su rivista]
Mutti, M.; Cordella, S.; Parisotto, A.; Bettelli, F.; Morselli, M.; Cuoghi, A.; Bresciani, P.; Messerotti, A.; Gilioli, A.; Pioli, V.; Giusti, D.; Colaci, E.; Cassanelli, L.; Paolini, A.; Martinelli, S.; Maffei, R.; Riva, G.; Nasillo, V.; Sarti, M.; Trenti, T.; Comoli, P.; Tagliafico, E.; Manfredini, R.; Eccher, A.; Lagreca, I.; Barozzi, P.; Potenza, L.; Marasca, R.; Candoni, A.; Luppi, M.; Forghieri, F.
abstract

2023 - Preclinical Validation of an Advanced Therapy Medicinal Product Based on Cytotoxic T Lymphocytes Specific for Mutated Nucleophosmin (NPM1mut) for the Treatment of NPM1mut-Acute Myeloid Leukemia [Articolo su rivista]
De Cicco, Marica; Lagreca, Ivana; Basso, Sabrina; Barozzi, Patrizia; Muscianisi, Stella; Bianco, Alba; Riva, Giovanni; Di Vincenzo, Sara; Pulvirenti, Chiara; Sapuppo, Davide; Siciliano, Mariangela; Rosti, Vittorio; Candoni, Anna; Zecca, Marco; Forghieri, Fabio; Luppi, Mario; Comoli, Patrizia
abstract

2023 - Prognostic Relevance of Multi-Antigenic Myeloma-Specific T-Cell Assay in Patients with Monoclonal Gammopathies [Articolo su rivista]
Lagreca, Ivana; Nasillo, Vincenzo; Barozzi, Patrizia; Castelli, Ilaria; Basso, Sabrina; Castellano, Sara; Paolini, Ambra; Maccaferri, Monica; Colaci, Elisabetta; Vallerini, Daniela; Natali, Patrizia; Debbia, Daria; Pirotti, Tommaso; Ottomano, Anna Maria; Maffei, Rossana; Bettelli, Francesca; Giusti, Davide; Messerotti, Andrea; Gilioli, Andrea; Pioli, Valeria; Leonardi, Giovanna; Forghieri, Fabio; Bresciani, Paola; Cuoghi, Angela; Morselli, Monica; Manfredini, Rossella; Longo, Giuseppe; Candoni, Anna; Marasca, Roberto; Potenza, Leonardo; Tagliafico, Enrico; Trenti, Tommaso; Comoli, Patrizia; Luppi, Mario; Riva, Giovanni
abstract

: Multiple Myeloma (MM) typically originates from underlying precursor conditions, known as Monoclonal Gammopathy of Undetermined Significance (MGUS) and Smoldering Multiple Myeloma (SMM). Validated risk factors, related to the main features of the clonal plasma cells, are employed in the current prognostic models to assess long-term probabilities of progression to MM. In addition, new prognostic immunologic parameters, measuring protective MM-specific T-cell responses, could help to identify patients with shorter time-to-progression. In this report, we described a novel Multi-antigenic Myeloma-specific (MaMs) T-cell assay, based on ELISpot technology, providing simultaneous evaluation of T-cell responses towards ten different MM-associated antigens. When performed during long-term follow-up (mean 28 months) of 33 patients with either MGUS or SMM, such deca-antigenic myeloma-specific immunoassay allowed to significantly distinguish between stable vs. progressive disease (p < 0.001), independently from the Mayo Clinic risk category. Here, we report the first clinical experience showing that a wide (multi-antigen), standardized (irrespective to patients' HLA), MM-specific T-cell assay may routinely be applied, as a promising prognostic tool, during the follow-up of MGUS/SMM patients. Larger studies are needed to improve the antigenic panel and further explore the prognostic value of MaMs test in the risk assessment of patients with monoclonal gammopathies.

2022 - Adverse outcome associated with daratumumab-based treatments in relapsed/refractory multiple myeloma patients with amplification of chromosome arm 1q21: a single-center retrospective experience [Articolo su rivista]
Barbieri, Emiliano; Maccaferri, Monica; Leonardi, Giovanna; Giacobbi, Francesca; Corradini, Giorgia; Lagreca, Ivana; Barozzi, Patrizia; Potenza, Leonardo; Marasca, Roberto; Luppi, Mario
abstract

2020 - Epidemiology and clinical outcomes of latent tuberculosis infection in adults affected with acute leukemia or aplastic anemia: a retrospective single-center study [Articolo su rivista]
Bettelli, F.; Giusti, D.; Morselli, M.; Colaci, E.; Nasillo, V.; Pioli, V.; Gilioli, A.; Iotti, S.; Galassi, L.; Giubbolini, R.; Colasante, C.; Catellani, H.; Barozzi, P.; Lagreca, I.; Vallerini, D.; Maffei, R.; Franceschini, E.; Mussini, C.; Banchelli, F.; D'Amico, R.; Marasca, R.; Narni, F.; Potenza, L.; Comoli, P.; Luppi, M.; Forghieri, F.
abstract

2019 - Characterization and dynamics of specific T cells against nucleophosmin-1 (NPM1)-mutated peptides in patients with NPM1-mutated acute myeloid leukemia [Articolo su rivista]
Forghieri, Fabio; Riva, Giovanni; Lagreca, Ivana; Barozzi, Patrizia; Vallerini, Daniela; Morselli, Monica; Paolini, Ambra; Bresciani, Paola; Colaci, Elisabetta; Maccaferri, Monica; Gilioli, Andrea; Nasillo, Vincenzo; Messerotti, Andrea; Pioli, Valeria; Arletti, Laura; Giusti, Davide; Bettelli, Francesca; Celli, Melania; Donatelli, Francesca; Corradini, Giorgia; Basso, Sabrina; Gurrado, Antonella; Cellini, Monica; Trenti, Tommaso; Marasca, Roberto; Narni, Franco; Martelli, Maria Paola; Falini, Brunangelo; Potenza, Leonardo; Luppi, Mario; Comoli, Patrizia
abstract

Nucleophosmin(NPM1)-mutated protein, a leukemia-specific antigen, represents an ideal target for AML immunotherapy. We investigated the dynamics of NPM1-mutated-specific T cells on PB and BM samples, collected from 31 adult NPM1-mutated AML patients throughout the disease course, and stimulated with mixtures of 18 short and long peptides (9-18mers), deriving from the complete C-terminal of the NPM1-mutated protein. Two 9-mer peptides, namely LAVEEVSLR and AVEEVSLRK (13.9-14.9), were identified as the most immunogenic epitopes. IFNγ-producing NPM1-mutated-specific T cells were observed by ELISPOT assay after stimulation with peptides 13.9-14.9 in 43/85 (50.6%) PB and 34/80 (42.5%) BM samples. An inverse correlation between MRD kinetics and anti-leukemic specific T cells was observed. Cytokine Secretion Assays allowed to predominantly and respectively identify Effector Memory and Central Memory T cells among IFNγ-producing and IL2-producing T cells. Moreover, NPM1-mutated-specific CTLs against primary leukemic blasts or PHA-blasts pulsed with different peptide pools could be expanded ex vivo from NPM1-mutated AML patients or primed in healthy donors. We describe the spontaneous appearance and persistence of NPM1-mutated-specific T cells, which may contribute to the maintenance of long-lasting remissions. Future studies are warranted to investigate the potential role of both autologous and allogeneic adoptive immunotherapy in NPM1-mutated AML patients.

2018 - Effectiveness of originator (Neupogen) and biosimilar (Zarzio) filgrastim in autologous peripheral blood stem cell mobilization in adults with acute myeloid leukemia: a single-center retrospective study [Articolo su rivista]
Nasillo, Vincenzo; Paolini, Ambra; Riva, Giovanni; Morselli, Monica; Potenza, Leonardo; Coluccio, Valeria; Maccaferri, Monica; Colaci, Elisabetta; Fantuzzi, Valeria; Messerotti, Andrea; Arletti, Laura; Pioli, Valeria; Lugli, Elisabetta; Gilioli, Andrea; Quadrelli, Chiara; Zucchini, Patrizia; Vallerini, Daniela; Lagreca, Ivana; Barozzi, Patrizia; Cuoghi, Angela; Bresciani, Paola; Marasca, Roberto; Mariano, Maria Teresa; Ceccherelli, Giovanni; Comoli, Patrizia; Campioli, Daniele; Trenti, Tommaso; Narni, Franco; Luppi, Mario; Forghieri, Fabio
abstract

n.d.

2017 - BCR-ABL-specific T-cell therapy in Ph+ ALL patients on tyrosine-kinase inhibitors [Articolo su rivista]
Comoli, Patrizia; Basso, Sabrina; Riva, Giovanni; Barozzi, Patrizia; Guido, Ilaria; Gurrado, Antonella; Quartuccio, Giuseppe; Rubert, Laura; Lagreca, Ivana; Vallerini, Daniela; Forghieri, Fabio; Morselli, Monica; Bresciani, Paola; Cuoghi, Angela; Paolini, Ambra; Colaci, Elisabetta; Marasca, Roberto; Cuneo, Antonio; Iughetti, Lorenzo; Trenti, Tommaso; Narni, Franco; Foà, Robin; Zecca, Marco; Luppi, Mario; Potenza, Leonardo
abstract

Although the emergence of bone marrow (BM)-resident (p190)BCR-ABL-specific T lymphocytes has been correlated with hematologic and cytogenetic remissions in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) undergoing maintenance tyrosine-kinase inhibitor treatment, little is known about the possibility of culturing these cells ex vivo and using them in T-cell therapy strategies. We investigated the feasibility of expanding/priming (p190)BCR-ABL-specific T cells in vitro by stimulation with dendritic cells pulsed with (p190)BCR-ABL peptides derived from the BCR-ABL junctional region and alternative splicing, and of adoptively administering them to patients with relapsed disease. We report on the feasibility of producing clinical-grade BCR-ABL-specific cytotoxic T lymphocytes (CTLs), endowed with antileukemia activity, from Ph(+) ALL patients and healthy donors. We treated 3 patients with Ph(+) ALL with autologous or allogeneic (p190)BCR-ABL-specific CTLs. No postinfusion toxicity was observed, except for a grade II skin graft-versus-host disease in the patient treated for hematologic relapse. All patients achieved a molecular or hematologic complete remission (CR) after T-cell therapy, upon emergence of (p190)BCR-ABL-specific T cells in the BM. Our results show that (p190)BCR-ABL-specific CTLs are capable of controlling treatment-refractory Ph(+) ALL in vivo, and support the development of adoptive immunotherapeutic approaches with BCR-ABL CTLs in Ph(+) ALL.

2017 - Detection of Fusarium-specific T cells in hematologic patients with invasive fusariosis [Articolo su rivista]
Vallerini, Daniela; Forghieri, Fabio; Lagreca, Ivana; Riva, Giovanni; Barozzi, Patrizia; Quadrelli, Chiara; Morselli, Monica; Bresciani, Paola; Cuoghi, Angela; Coluccio, Valeria; Maccaferri, Monica; Paolini, Ambra; Colaci, Elisabetta; Marasca, Roberto; Narni, Franco; Cellini, Monica; Beauvais, Anne; Latgè, Jean Paul; Romani, Luigina; Iughetti, Lorenzo; Comoli, Patrizia; Campioli, Daniele; Trenti, Tommaso; Luppi, Mario; Potenza, Leonardo
abstract

N.A.

2016 - All-trans retinoic acid (ATRA) in non-promyelocytic acute myeloid leukemia (AML): results of combination of ATRA with low-dose Ara-C in three elderly patients with NPM1-mutated AML unfit for intensive chemotherapy and review of the literature [Articolo su rivista]
Forghieri, Fabio; Bigliardi, Sara; Quadrelli, Chiara; Morselli, Monica; Potenza, Leonardo; Paolini, Ambra; Colaci, Elisabetta; Barozzi, Patrizia; Zucchini, Patrizia; Riva, Giovanni; Vallerini, Daniela; Lagreca, Ivana; Marasca, Roberto; Narni, Franco; Venditti, Adriano; Martelli, Maria Paola; Falini, Brunangelo; Lo Coco, Francesco; Amadori, Sergio; Luppi, Mario
abstract

Based upon the clinical behavior of three patients, we suggest that the combination of low-dose Ara-C and all-trans retinoic acid may potentially be effective in some elderly patients, unfit for intensive chemotherapy, affected with NPM1-mutated acute myeloid leukemia without FLT3 mutations, warranting perspective clinical studies in these selected patients.

2016 - Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV6 [Articolo su rivista]
Barozzi, Patrizia; Riva, Giovanni; Vallerini, Daniela; Quadrelli, Chiara; Lagreca, Ivana; Eccheli, Roberta; Forghieri, Fabio; Coluccio, Valeria; Maccaferri, Monica; Paolini, Ambra; Colaci, Elisabetta; Morselli, Monica; Marasca, Roberto; Narni, Franco; Potenza, Leonardo; Luppi, Mario; Comoli, Patrizia; Campioli, Daniele; Trenti, Tommaso
abstract

Circulating functional T cells specific to human herpes virus 6 (HHV6) antigens in individuals with chromosomally integrated HHV6

2016 - PEGylated siRNA lipoplexes for silencing of BLIMP-1 in Primary Effusion Lymphoma: In vitro evidences of antitumoral activity [Articolo su rivista]
Belletti, Daniela; Tosi, Giovanni; Forni, Flavio; Lagreca, Ivana; Barozzi, Patrizia; Pederzoli, Francesca; Vandelli, Maria Angela; Riva, Giovanni; Luppi, Mario; Ruozi, Barbara
abstract

Silencing of the B lymphocyte-induced maturation protein 1 (Blimp-1), a pivotal transcriptional regulator during terminal differentiation of B cells into plasma cells with siRNAs is under investigation as novel therapeutic approach in Primary Effusion Lymphoma (PEL), a HHV-8 related and aggressive B cell Lymphoma currently lacking of an efficacious therapeutic approach. The clinical application of small interfering RNA (siRNA) in cancer therapy is limited by the lack of an efficient systemic siRNA delivery system. In this study we aim to develop pegylated siRNA lipoplexes formed using the cationic lipid DOTAP and DSPE-PEG2000, capable to effectively stabilize anti-Blimp-1 siRNA and suitable for systemic administration. Two types of pegylated lipoplexes using a classic (C-PEG Lipoplexes) or a post-pegylation method (P-PEG-Lipoplexes) were formulated and compared in their physicochemical properties (size, zeta potential, morphology and structure) and efficiency on PEL cell lines. A stable siRNAs protection was obtained with post pegylation approach (2% molar of DSPE-PEG2000 with respect to lipid) resulting in structures with diameters of 300 nm and a complexation efficiency higher that 80% (0.08 nmol/10 nmol of lipid). In vitro studies on PEL cell lines suggested that empty liposomes were characterized by a low cell toxicity also after PEG modification (cell viability and cell density over 85% after treatment with 10 μM of lipid). We demonstrated that P-PEG-Lipoplexes were able to significantly reduce the levels of BLIMP-1 protein leading to reduction of viability (less that 15% after transfection with 100 nM of complexed siRNAs) and activation of apoptosis. In vitro efficiency encourages us to further test the in vivo potential of P-PEG-Lipoplexes in PEL therapy.

2016 - The bone marrow represents an enrichment site of specific T lymphocytes against filamentous fungi [Articolo su rivista]
Vallerini, Daniela; Riva, Giovanni; Barozzi, Patrizia; Forghieri, Fabio; Lagreca, Ivana; Quadrelli, Chiara; Morselli, Monica; Bresciani, Paola; Cuoghi, Angela; Coluccio, Valeria; Maccaferri, Monica; Paolini, Ambra; Colaci, Elisabetta; Marasca, Roberto; Narni, Franco; Latgè, Jean Paul; Romani, Luigina; Comoli, Patrizia; Campioli, Daniele; Trenti, Tommaso; Luppi, Mario; Potenza, Leonardo
abstract

Bone marrow has already been described as an enrichment site for several antigen-specific T lymphocytes, but the presence of mould-specific T cells has never been investigated in the bone marrow. We have previously demonstrated that mould-specific T cells emerge in the peripheral blood of patients with invasive fungal infections (IFI) but tend to become undetectable after disease resolution. In seven patients with a history of IFI, we investigated the presence of mould-specific T cells secreting different cytokines in bone marrow and peripheral blood paired samples. The results showed that the frequencies of mould-specific T cells secreting the protective cytokine IFNI3 are significantly higher in bone marrow (BM) and are mainly represented by CD8+ T lymphocytes with effector phenotype. A putative disappearance of such protective BM responses after myeloablative therapy could contribute to the increased risk of IFI in hematologic patients.

2015 - Antineoplastic effects of liposomal siRNA treatment targeting BLIMP1/PRDM1 in primary effusion lymphoma [Articolo su rivista]
Riva, Giovanni; Lagreca, Ivana; Mattiolo, Adriana; Belletti, Daniela; Lignitto, Laura; Barozzi, Patrizia; Ruozi, Barbara; Vallerini, Daniela; Quadrelli, Chiara; Corradini, Giorgia; Forghieri, Fabio; Marasca, Roberto; Narni, Franco; Tosi, Giovanni; Forni, Flavio; Vandelli, Maria Angela; Amadori, Alberto; Chieco Bianchi, Luigi; Potenza, Leonardo; Calabro', Maria Luisa; Luppi, Mario
abstract

RNA interference (RNAi) has been suggested to represent a promising therapeutic approach in different disease settings. Primary effusion lymphoma (PEL) is a plasmablastic lymphoma consistently expressing B lymphocyte-induced maturation protein 1 (Blimp-1), a pivotal transcriptional regulator during terminal differentiation of B cells into plasma cells. Here we report, for the first time, that transient knockdown of the BLIMP1 gene (also known as PR Domain Containing 1 with ZNF Domain, or PRDM1) using small interfering RNA (siRNA) delivered by liposomes, induced remarkable killing in PEL cell lines. Furthermore, in a murine model of PEL, significantly prolonged survival was achieved by intraperitoneal treatment with such anti-BLIMP1 lipoplexes, while no vector-induced toxicity was observed. This effective and safe RNAi strategy, based on liposomal siRNA targeting a master transcription factor of post-germinal center B cells, may indeed be a potential treatment against plasmablastic lymphoma

2015 - Epidemiology and clinical outcome of lower respiratory tract infections by respiratory syncytial virus or parainfluenza virus type 3 in adults receiving treatment for either acute leukemia or severe aplastic anemia: a retrospective single center study [Articolo su rivista]
Bigliardi, Sara; Morselli, Monica; Potenza, Leonardo; Riva, Giovanni; Coluccio, Valeria; Maccaferri, Monica; Paolini, Ambra; Colaci, Elisabetta; Fantuzzi, Valeria; Soci, Francesco; Nasillo, Vincenzo; Messerotti, Andrea; Arletti, Laura; Pioli, Valeria; Lugli, Elisabetta; Gilioli, Andrea; Quadrelli, Chiara; Vallerini, Daniela; Barozzi, Patrizia; Lagreca, Ivana; Marasca, Roberto; Narni, Franco; Franceschini, Erica; Codeluppi, Mauro; Mussini, Cristina; Luppi, Mario; Forghieri, Fabio
abstract

Epidemiology and clinical outcome of lower respiratory tract infections by respiratory syncytial virus or parainfluenza virus type 3 in adults receiving treatment for either acute leukemia or severe aplastic anemia: a retrospective single center study

2015 - NPM1 mutations may reveal acute myeloid leukemia in cases otherwise morphologically diagnosed as myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms [Articolo su rivista]
Forghieri, Fabio; Paolini, Ambra; Morselli, Monica; Bigliardi, Sara; Bonacorsi, Goretta; Leonardi, Giovanna; Coluccio, Valeria; Maccaferri, Monica; Fantuzzi, Valeria; Faglioni, Laura; Colaci, Elisabetta; Soci, Francesco; Nasillo, Vincenzo; Messerotti, Andrea; Arletti, Laura; Pioli, Valeria; Zucchini, Patrizia; Quadrelli, Chiara; Corradini, Giorgia; Giacobbi, Francesca; Vallerini, Daniela; Riva, Giovanni; Barozzi, Patrizia; Lagreca, Ivana; Marasca, Roberto; Narni, Franco; Mecucci, Cristina; Ottaviani, Emanuela; Martinelli, Giovanni; Falini, Brunangelo; Luppi, Mario; Potenza, Leonardo
abstract

NPM1 mutations may reveal acute myeloid leukemia in cases otherwise morphologically diagnosed as myelodysplastic syndromes or myelodysplastic/myeloproliferative neoplasms.

2015 - Nutlin-3 loaded nanocarriers: Preparation, characterization and in vitro antineoplastic effect against primary effusion lymphoma [Articolo su rivista]
Belletti, Daniela; Tosi, Giovanni; Riva, Giovanni; Lagreca, Ivana; Galliania, M; Luppi, Mario; Vandelli, Maria Angela; Forni, Flavio; Ruozi, Barbara
abstract

In this investigation, Nutlin-3 (Nut3), a novel antitumor drug with low water solubility (<0.1mg/L at 25°C), was loaded into liposomes (Lipo-Nut3), polymeric nanoparticles (NPs-Nut3) and nanoparticles engineered with an antibody direct against Syndecan-1/CD 138 (Syn-NPs-Nut3) to obtain carriers targeted to PEL (primary effusion lymphoma). The physicochemical properties of these carriers were determined. Atomic force microscopy showed that all the particles were well formed and spherical in shape. The presence of the antibody on surface led to a significant increase of mean diameter (280 ± 63 nm), PDI (0.3) and the shift of zeta potential towards neutrality (-1 mV). The entrapment efficiency of Lipo-Nut3, NPs-Nut3 and Syn-NPs-Nut3 was 30, 52 and 29%, and drug loading was 1.4, 4.5 and 2.6%, respectively. By performing cytofluorimetric analyses and bromodeoxyuridine (BrdU) assay, the efficacy of nanocarriers to deliver the antineoplastic drug into a PEL cell line namely BCBL-1 (immortalized body cavity B-cell lymphoma) was investigated. Two days after the treatment with 20 μM of Syn-NPs-Nut3, the cell density decreased at about 60% while the cell viability decreased at 56% only 5 days after transfection, when compared with untreated cells. A cell cycle arrest was observed with a significant decrease of cells in S-phase and increasing of apoptotic cell, if compared with untreated control. These results confirms the potential of nanocarriers approaches to deliver antitumor drug with unfavorable chemico-physical properties. Moreover, this study strongly suggests that Syn-NPs-Nut3 can be a valuable drug carrier system for the treatment of PEL lymphoma.

2014 - Long-term molecular remission with persistence of BCR-ABL1-specific cytotoxic T cells following imatinib withdrawal in an elderly patient with Philadelphia-positive ALL [Articolo su rivista]
Riva, Giovanni; Luppi, Mario; Lagreca, Ivana; Barozzi, Patrizia; Quadrelli, Chiara; Vallerini, Daniela; Zanetti, Eleonora; Basso, Sabrina; Forghieri, Fabio; Morselli, Monica; Maccaferri, Monica; Paolini, Ambra; Fantuzzi, Valeria; Messerotti, Andrea; Maffei, Rossana; Iacobucci, Ilaria; Martinelli, Giovanni; Marasca, Roberto; Narni, Franco; Comoli, Patrizia; Potenza, Leonardo
abstract

Long-term molecular remission with persistence of BCR-ABL1-specific cytotoxic T cells following imatinib withdrawal in an elderly patient with Philadelphia-positive ALL

2013 - siRNA-BASED THERAPEUTICS: DELIVERY AND TARGETING TO PEL TUMOR BY USING CATIONIC LIPOSOMES [Abstract in Atti di Convegno]
Belletti, Daniela; Riva, Giovanni; Tosi, Giovanni; Lagreca, Ivana; Barozzi, Patrizia; Adriana, Mattiolo; Elena, Negri; Laura, Lignitto; Luigi Chieco, Bianchi; Forni, Flavio; Luppi, Mario; Vandelli, Maria Angela; Maria Luisa, Calabrò; Ruozi, Barbara
abstract

Aims of this research was to develop a “nanomedicine” approach based on siRNA delivery for the treatment of primary effusion lymphoma (PEL). The therapeutic use of antitumoral siRNA requires the development of specifically designed functional vectors, allowing improve¬ment of siRNA stability after systemic admin¬istration, and enabling targeted delivery directly into the neoplastic cells. In this context, liposomes, and particularly cationic liposomes, appears particu¬larly suitable to generate complexes with highly degradable siRNAs, as well as to specifically deliver siRNAs directly into the cytoplasm of the target tumor cells, where RNA interference processes take place. Generally, the electrostatic interaction between the positively charged lipids and the negatively charged nucleic acids leads to the formation of stable lipoplexes, protecting the cargo against nuclease attack and improving the cellular uptake and activity [1. In this context, we are investigating innovative target strategies to improve the treatment of human herpesvirus 8 (HHV8)-associated primary effusion lymphoma (PEL). Primary effusion lymphoma (PEL) is an aggressive B cell non-Hodgkin’s lymphoma, affecting the serous cavities (such as the pleu¬ral, pericardial and abdominal cavities) and preferentially arising in immunocompromised or elderly patients, typically affected by several comorbidities and organ function impairments. PEL therapy has been revealed to be unsuccessful in the vast majority of patients, who are invariably characterized by a poor prognoses. Recently, small interfering RNAs (siRNAs), able to knock-down viral oncogenic proteins, were shown to induce efficient PEL cell apoptosis in vitro and PEL regressions in mice treated with intracavitary injection of lentiviral vectors expressing siRNA precursors[2. Moving from our promising preliminary results in the field of nanotechnologies[3-4, we are developing different lipid-based nanocarriers (cationic and stealth-cationic liposomes), to deliver specific siRNAs to knock-down novel molecular targets (HHV8-encoded microRNAs, viral oncogenic proteins, or host transcription factors) with relevant functions in PEL pathogenesis [5. We are presently testing the delivery efficiency of these nanocarriers and the antineoplastic activity in vitro and in vivo using different PEL-derived cell lines and a previously established PEL mouse model[6. We performed several preliminary technological experiments aimed at optimizing the operative condition to obtain the efficient liposomes/siRNAs complexes. Chemic-physical properties of both liposomes and lipoplexes were evaluated by exploiting microscopic, spectroscopic and gel electrophoresis techniques. In vitro experiments demonstrated a high transfection efficiency of some of our carriers, which stably protected and efficaciously delivered siRNAs into PEL cells. Preliminary experiments using a mixture of siRNAs targeting a specific cellular gene showed a remarkable dose-dependent apoptosis, measured by annexin-V staining, in lipoplexes-transfected PEL cells. Moreover, the in vivo delivery of these therapeutic siRNAs significantly increased the survival time of treated mice compared with control treatment (log-rank test, lipoplexes vs empty liposomes, p=0.002), indicating that our lipoplexes exerted a significant antineoplastic activity. The empty carriers were not toxic in control mice and did not delay PEL development respect untraeted mice. Our data indicate that our lipoplexes may therefore be considered as the basis for the development of useful short interfering RNA delivery vectors to treat PEL tumor. Moreover, we identified a target gene whose suppression exerts a relevant tumoricidal activity on PEL cells in vitro and in vivo, opening new perspectives for PEL treatment.