14 results on '"Montini E"'
Search Results
2. HIV-1 mediated insertional activation of STAT5B and BACH2 promotes the formation of a viral reservoir in T regulatory cells
- Author
-
Cesana, D., primary, Santoni de Sio, F., additional, Rudilosso, L., additional, Gallina, P., additional, Calabria, A., additional, Bruzzesi, E., additional, Passerini, L., additional, Nozza, S., additional, Vicenzi, E., additional, Poli, G., additional, Gregori, S., additional, Tambussi, G., additional, and Montini, E., additional
- Published
- 2017
- Full Text
- View/download PDF
3. Preclinical evaluation of donor-derived sleeping beauty modified CD19CAR+ lymphocytes for the treatment of acute lymphoblastic leukemia
- Author
-
Magnani, C., primary, Mezzanotte, C., additional, Cappuzzello, C., additional, Benedicenti, F., additional, Belotti, D., additional, Cabiati, B., additional, Bardini, M., additional, Fazio, G., additional, Cazzaniga, G., additional, Cooper, L., additional, Montini, E., additional, Gaipa, G., additional, Biondi, A., additional, and Biagi, E., additional
- Published
- 2017
- Full Text
- View/download PDF
4. HIV-1 mediated insertional activation of STAT5B promotes the formation of a viral reservoir in T regulatory cells
- Author
-
Cesana, D., primary, de Sio, F.R. Santoni, additional, Rudilosso, L., additional, Gallina, P., additional, Calabria, A., additional, Passerini, L., additional, Nozza, S., additional, Vicenzi, E., additional, Poli, G., additional, Tambussi, G., additional, and Montini, E., additional
- Published
- 2015
- Full Text
- View/download PDF
5. Cytokine-induced killer (CIK) cells engineered with chimeric antigen receptors (CARs) by sleeping beauty system
- Author
-
Magnani, C., primary, Turazzi, N., additional, Benedicenti, F., additional, Tettamanti, S., additional, Attianese, G. Giordano, additional, Rossi, V., additional, Montini, E., additional, Cooper, L., additional, Aiuti, A., additional, Biondi, A., additional, and Biagi, E., additional
- Published
- 2014
- Full Text
- View/download PDF
6. Argatroban for treatment of vein thrombosis complicating heparin-induced thrombocytopenia in haemodialyzed multiple myeloma: a case report
- Author
-
Pierfranceschi, M. Giorgi, primary, Orlando, S., additional, Chiesa, S., additional, Barbera, M., additional, Montini, E., additional, Lombardi, F., additional, Rossini, P., additional, Bologna, G., additional, and Bacciu, S.A., additional
- Published
- 2012
- Full Text
- View/download PDF
7. GMP production of anti-tumor cytotoxic T-cell lines for adoptive T-cell therapy in patients with solid neoplasia
- Author
-
Turin, I., primary, Pedrazzoli, P., additional, Tullio, C., additional, Montini, E., additional, Carmela La Grotteria, M., additional, Schiavo, R., additional, Perotti, C., additional, Locatelli, F., additional, Carretto, E., additional, Maccario, R., additional, Siena, S., additional, and Montagna, D., additional
- Published
- 2007
- Full Text
- View/download PDF
8. Vinorelbine (VNB) plus raltritexed in advanced breast cancer (ABC), a phase II study. Preliminary results
- Author
-
Ferrari, V.D., primary, Marpicati, P., additional, Montini, E., additional, Rangoni, G., additional, Simoncini, E., additional, and Marinl, G., additional
- Published
- 1999
- Full Text
- View/download PDF
9. L-folinic acid and 5-fluorouracil in the treatment of advanced breast cancer: A phase II study
- Author
-
Zaniboni, A., primary, Meriggi, F., additional, Arcangeli, G., additional, Marpicati, P., additional, Montini, E., additional, Simoncini, E., additional, and Marini, G., additional
- Published
- 1993
- Full Text
- View/download PDF
10. Multiple Integrated Non-clinical Studies Predict the Safety of Lentivirus-Mediated Gene Therapy for β-Thalassemia
- Author
-
Francesca Sanvito, Ylenia Paleari, Annamaria Aprile, Franck Chanut, Luigi Naldini, Fulvio Mavilio, Patrizia Cristofori, Claudia Rossi, Maria Rosa Lidonnici, Giuliana Ferrari, Giacomo Mandelli, Eugenio Montini, Andrea Calabria, Alessandro Ambrosi, Valentina Poletti, Francesca Tiboni, Michela Vezzoli, Carsten W. Lederer, Universita Vita Salute San Raffaele = Vita-Salute San Raffaele University [Milan, Italie] (UniSR), Pierantoni-Morgagni Hospital, Partenaires INRAE, Approches génétiques intégrées et nouvelles thérapies pour les maladies rares (INTEGRARE), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Généthon, Généthon, École Pratique des Hautes Études (EPHE), Lidonnici, M. R., Paleari, Y., Tiboni, F., Mandelli, G., Rossi, C., Vezzoli, M., Aprile, A., Lederer, C. W., Ambrosi, A., Chanut, F., Sanvito, F., Calabria, A., Poletti, V., Mavilio, F., Montini, E., Naldini, L., Cristofori, P., and Ferrari, G.
- Subjects
safety ,0301 basic medicine ,thalassemia ,lcsh:QH426-470 ,[SDV]Life Sciences [q-bio] ,Genetic enhancement ,biodistribution ,gene therapy ,genotoxicity ,hematopoiesis ,hematopoietic stem cell ,integration site ,lentiviral vector ,preclinical model ,Article ,Viral vector ,03 medical and health sciences ,Genetics ,medicine ,lcsh:QH573-671 ,Molecular Biology ,Gene ,thalassemia gene therapy hematopoiesis hematopoietic stem cell preclinical model safety lentiviral vector biodistribution genotoxicity integration site ,biology ,lcsh:Cytology ,Hematopoietic stem cell ,biology.organism_classification ,3. Good health ,Clinical trial ,lcsh:Genetics ,Haematopoiesis ,030104 developmental biology ,medicine.anatomical_structure ,hematopoiesi ,Lentivirus ,Cancer research ,Molecular Medicine ,Stem cell - Abstract
Gene therapy clinical trials require rigorous non-clinical studies in the most relevant models to assess the benefit-to-risk ratio. To support the clinical development of gene therapy for β-thalassemia, we performed in vitro and in vivo studies for prediction of safety. First we developed newly GLOBE-derived vectors that were tested for their transcriptional activity and potential interference with the expression of surrounding genes. Because these vectors did not show significant advantages, GLOBE lentiviral vector (LV) was elected for further safety characterization. To support the use of hematopoietic stem cells (HSCs) transduced by GLOBE LV for the treatment of β-thalassemia, we conducted toxicology, tumorigenicity, and biodistribution studies in compliance with the OECD Principles of Good Laboratory Practice. We demonstrated a lack of toxicity and tumorigenic potential associated with GLOBE LV-transduced cells. Vector integration site (IS) studies demonstrated that both murine and human transduced HSCs retain self-renewal capacity and generate new blood cell progeny in the absence of clonal dominance. Moreover, IS analysis showed an absence of enrichment in cancer-related genes, and the genes targeted by GLOBE LV in human HSCs are well known sites of integration, as seen in other lentiviral gene therapy trials, and have not been associated with clonal expansion. Taken together, these integrated studies provide safety data supporting the clinical application of GLOBE-mediated gene therapy for β-thalassemia. Keywords: thalassemia, gene therapy, hematopoiesis, hematopoietic stem cell, preclinical model, safety, lentiviral vector, biodistribution, genotoxicity, integration site
- Published
- 2018
11. Cyclosporin A and Rapamycin Relieve Distinct Lentiviral Restriction Blocks in Hematopoietic Stem and Progenitor Cells
- Author
-
Eugenio Montini, Daniela Cesana, Carolina Petrillo, Luigi Naldini, Anna Kajaste-Rudnitski, Francesco Piras, Sara Bartolaccini, Petrillo, C., Cesana, D., Piras, F., Bartolaccini, S., Naldini, L., Montini, E., and Kajaste-Rudnitski, A.
- Subjects
Genetic enhancement ,Cellular differentiation ,Transgene ,Genetic Vectors ,CD34 ,Gene Expression ,Biology ,Immunophenotyping ,Mice ,Transduction (genetics) ,Transduction, Genetic ,Cyclosporin a ,Drug Discovery ,Genetics ,Animals ,Humans ,Transgenes ,Progenitor cell ,Molecular Biology ,Sirolimus ,Pharmacology ,Graft Survival ,Lentivirus ,Hematopoietic Stem Cell Transplantation ,Cell Differentiation ,Fetal Blood ,Hematopoietic Stem Cells ,Cell biology ,Haematopoiesis ,Phenotype ,Immunology ,Cyclosporine ,Molecular Medicine ,Original Article - Abstract
Improving hematopoietic stem and progenitor cell (HSPC) permissiveness to HIV-derived lentiviral vectors (LVs) remains a challenge for the field of gene therapy as high vector doses and prolonged ex vivo culture are still required to achieve clinically relevant transduction levels. We report here that Cyclosporin A (CsA) and Rapamycin (Rapa) significantly improve LV gene transfer in human and murine HSPC. Both compounds increased LV but not gammaretroviral transduction and acted independently of calcineurin and autophagy. Improved gene transfer was achieved across all CD34(+) subpopulations, including in long-term SCID repopulating cells. Effects of CsA were specific of HSPC and opposite to its known impact on HIV replication. Mutating the Cyclophilin A binding pocket of the viral capsid (CA) further improved transduction in combination with CsA. Tracking of the LV genome fate revealed that CsA relieves a CA-dependent early block and increases integration, while Rapa acts early in LV infection independently of the viral CA. In agreement, only Rapa was able to improve transduction by an integrase-defective LV harboring wild-type CA. Overall, our findings pave the way for more efficient and sustainable LV gene therapy in human HSPCs and shed light on the multiple innate barriers specifically hampering LV transduction in these cells.
- Published
- 2015
- Full Text
- View/download PDF
12. Precise Gene Editing Preserves Hematopoietic Stem Cell Function following Transient p53-Mediated DNA Damage Response
- Author
-
Raffaella Di Micco, Giulia Schiroli, Valentina Vavassori, Anastasia Conti, Pietro Genovese, Delphine Ndiaye-Lobry, Patrizia Gasparini, Julie Chaumeil, Chiara Brombin, Lucrezia della Volpe, Ivan Merelli, Aurelien Jacob, Eugenio Montini, Andrea Calabria, Samuele Ferrari, Luigi Naldini, Stefano Beretta, Luisa Albano, Eralda Salataj, Schiroli, Giulia, Conti, Anastasia, Ferrari, Samuele, Della Volpe, Lucrezia, Jacob, Aurelien, Albano, Luisa, Beretta, Stefano, Calabria, Andrea, Vavassori, Valentina, Gasparini, Patrizia, Salataj, Eralda, Ndiaye-Lobry, Delphine, Brombin, Chiara, Chaumeil, Julie, Montini, Eugenio, Merelli, Ivan, Genovese, Pietro, Naldini, Luigi, Di Micco, Raffaella, Schiroli, G, Conti, A, Ferrari, S, della Volpe, L, Jacob, A, Albano, L, Beretta, S, Calabria, A, Vavassori, V, Gasparini, P, Salataj, E, Ndiaye-Lobry, D, Brombin, C, Chaumeil, J, Montini, E, Merelli, I, Genovese, P, Naldini, L, and Di Micco, R
- Subjects
DNA damage ,DNA repair ,adeno-associated vector ,Mice, SCID ,Biology ,DNA damage response ,Cell Line ,DNA double strand break ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Genome editing ,Mice, Inbred NOD ,K562 Cell ,Genetics ,medicine ,genome editing ,Animals ,Humans ,CRISPR ,Progenitor cell ,programmable nuclease ,030304 developmental biology ,Gene Editing ,Mice, Knockout ,0303 health sciences ,Animal ,Cas9 ,Hematopoietic stem cell ,Hematopoietic Stem Cell ,Cell Biology ,Hematopoietic Stem Cells ,Cell biology ,hematopoietic stem and progenitor cell ,Haematopoiesis ,medicine.anatomical_structure ,Molecular Medicine ,DNA double strand breaks ,hematopoietic stem and progenitor cells ,p53 pathway ,programmable nucleases ,Tumor Suppressor Protein p53 ,K562 Cells ,030217 neurology & neurosurgery ,Human ,DNA Damage - Abstract
Precise gene editing in hematopoietic stem and progenitor cells (HSPCs) holds promise for treating genetic diseases. However, responses triggered by programmable nucleases in HSPCs are poorly characterized and may negatively impact HSPC engraftment and long-term repopulation capacity. Here, we induced either one or several DNA double-stranded breaks (DSBs) with optimized zinc-finger and CRISPR/Cas9 nucleases and monitored DNA damage response (DDR) foci induction, cell-cycle progression, and transcriptional responses in HSPC subpopulations, with up to single-cell resolution. p53-mediated DDR pathway activation was the predominant response to even single-nuclease-induced DSBs across all HSPC subtypes analyzed. Excess DSB load and/or adeno-associated virus (AAV)-mediated delivery of DNA repair templates induced cumulative p53 pathway activation, constraining proliferation, yield, and engraftment of edited HSPCs. However, functional impairment was reversible when DDR burden was low and could be overcome by transient p53 inhibition. These findings provide molecular and functional evidence for feasible and seamless gene editing in HSPCs. Precise gene editing has the potential to treat immune and hematological diseases. Genovese, Naldini, Di Micco, and colleagues now show that gene-editing procedures are well tolerated by hematopoietic stem cells and provide molecular evidence of the feasibility of seamless gene editing, strengthening translation of such approaches to humans.
- Published
- 2019
13. Challenges in Vector and Trial Design Using Retroviral Vectors for Long-Term Gene Correction in Hematopoietic Stem Cell Gene Therapy
- Author
-
Gösta Gahrton, Eugene Rosenthal, Linda Wolff, Luigi Naldini, Marina O'Reilly, Frederic D. Bushman, John A. Zaia, Nikunj V. Somia, Susan R. Ross, Odile Cohen-Haguenauer, Christof von Kalle, Hans-Peter Kiem, Hung Fan, Theodore Friedmann, Nancy M. P. King, Jacqueline Corrigan-Curay, Eugenio Montini, Donald B. Kohn, Robyn S. Shapiro, Brian P. Sorrentino, Harry L. Malech, Cynthia E. Dunbar, Alessandro Aiuti, Manuel J.T. Carrondo, Christopher Baum, Robert Jambou, Naomi Rosenberg, Corrigan Curay, J, Cohen Haguenauer, O, O'Reilly, M, Ross, Sr, Fan, H, Rosenberg, N, Somia, N, King, N, Friedmann, T, Dunbar, C, Aiuti, Alessandro, Naldini, Luigi, Baum, C, von Kalle, C, Kiem, Hp, Montini, E, Bushman, F, Sorrentino, Bp, Carrondo, M, Malech, H, Gahrton, G, Shapiro, R, Wolff, L, Rosenthal, E, Jambou, R, Zaia, J, and Kohn, D. B.
- Subjects
Genetic enhancement ,medicine.medical_treatment ,Genetic Vectors ,Disease ,Hematopoietic stem cell transplantation ,Bioinformatics ,Gene Transfer Techniques ,Humans ,Retroviridae ,Hematopoietic Stem Cell Transplantation ,Genetic Therapy ,Research Design ,03 medical and health sciences ,0302 clinical medicine ,Chronic granulomatous disease ,Drug Discovery ,Genetics ,Medicine ,Vector (molecular biology) ,Molecular Biology ,Immunodeficiency ,030304 developmental biology ,Settore MED/38 - Pediatria Generale e Specialistica ,Pharmacology ,0303 health sciences ,Severe combined immunodeficiency ,business.industry ,medicine.disease ,3. Good health ,Leukemia ,030220 oncology & carcinogenesis ,Immunology ,Molecular Medicine ,business - Abstract
Over the past two decades, incredible progress has been made using gene therapy for inherited severe immunodeficiency disorders, such as X-linked severe combined immunodeficiency disorder (SCID-X1) and adenosine deaminase deficiency–severe combined immunodeficiency disorder (ADA-SCID).1,2,3 However, for reasons that remain unclear, gene transfer for SCID-X1 has also been associated with some cases of vector-induced leukemia whereas no cases have been seen in the ADA-SCID trials despite the common use of g-retroviral vectors. The first case was reported in a French gene transfer trial for SCID-X1.4 Over the next six years, an additional three cases were reported in that trial and one in a second SCID-X1 trial that enrolled a combined total of 20 subjects.2 Unfortunately, genotoxicity would not remain confined to SCID-X1. Recent reports of insertional mutagenesis leading to myelodysplastic syndrome in a trial for chronic granulomatous disease and a case of leukemia in a trial for Wiskott-Aldrich syndrome (WAS), both of which used g-retroviral vectors, underscored that this type of toxicity can also apply to other disease settings.5,6,7 In all these cases, insertion of the g-retroviral vector near known proto-oncogenes led to enhancer-mediated expression of these proto-oncogenes.
- Published
- 2012
14. Lentiviral Vector Integration Profiles Differ in Rodent Postmitotic Tissues
- Author
-
A MacNeil, Ulrich Abel, Daniela Cesana, Christof von Kalle, Cynthia C. Bartholomae, Adrian J. Thrasher, Jens Uwe Appelt, Hanno Glimm, Eugenio Montini, Bernhard Korn, Anna Paruzynski, Luigi Naldini, Rafael J. Yáñez-Muñoz, Anne Arens, Steven J. Howe, Kamaljit S. Balaggan, Manfred Schmidt, Robin R. Ali, Bartholomae, Cc, Arens, A, Balaggan, K, Yanez Munoz, Rj, Montini, E, Howe, Sj, Paruzynski, A, Korn, B, Appelt, Ju, Macneil, A, Cesana, D, Abel, U, Glimm, H, Naldini, Luigi, Ali, Rr, Thrasher, Aj, von Kalle, C, and Schmidt, M.
- Subjects
Virus Integration ,Genetic enhancement ,Transgene ,Genetic Vectors ,Mitosis ,DNA, Satellite ,Biology ,Polymerase Chain Reaction ,Cell Line ,Viral vector ,Mice ,03 medical and health sciences ,PSIP1 ,0302 clinical medicine ,Commentaries ,Drug Discovery ,Genetics ,Animals ,Molecular Biology ,Gene ,Adaptor Proteins, Signal Transducing ,030304 developmental biology ,Pharmacology ,Mice, Inbred BALB C ,0303 health sciences ,Lentivirus ,Terminal Repeat Sequences ,Molecular biology ,Long terminal repeat ,Rats ,Cell culture ,Molecular Medicine ,Original Article ,Female ,030217 neurology & neurosurgery ,Ex vivo ,Transcription Factors - Abstract
Lentiviral vectors with self-inactivating (SIN) long terminal repeats (LTRs) are promising for safe and sustained transgene expression in dividing as well as quiescent cells. As genome organization and transcription substantially differs between actively dividing and postmitotic cells in vivo, we hypothesized that genomic vector integration preferences might be distinct between these biological states. We performed integration site (IS) analyses on mouse dividing cells (fibroblasts and hematopoietic progenitor cells (HPCs)) transduced ex vivo and postmitotic cells (eye and brain) transduced in vivo. As expected, integration in dividing cells occurred preferably into gene coding regions. In contrast, postmitotic cells showed a close to random frequency of integration into genes and gene spare long interspersed nuclear elements (LINE). Our studies on the potential mechanisms responsible for the detected differences of lentiviral integration suggest that the lowered expression level of Psip1 reduce the integration frequency in vivo into gene coding regions in postmitotic cells. The motif TGGAA might represent one of the factors for preferred lentiviral integration into mouse and rat Satellite DNA. These observations are highly relevant for the correct assessment of preclinical biosafety studies, indicating that lentiviral vectors are well suited for safe and effective clinical gene transfer into postmitotic tissues.
- Published
- 2011
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.