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20 results on '"Plati, Tiziana"'

1. Liver-directed lentiviral gene therapy corrects hemophilia A mice and achieves normal-range factor VIII activity in non-human primates

Author

Milani, Michela, Canepari, Cesare, Liu, Tongyao, Biffi, Mauro, Russo, Fabio, Plati, Tiziana, Curto, Rosalia, Patarroyo-White, Susannah, Drager, Douglas, Visigalli, Ilaria, Brombin, Chiara, Albertini, Paola, Follenzi, Antonia, Ayuso, Eduard, Mueller, Christian, Annoni, Andrea, Naldini, Luigi, and Cantore, Alessio

Published
2022
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3. MicroRNA-223 dose levels fine tune proliferation and differentiation in human cord blood progenitors and acute myeloid leukemia

Author

Gentner, Bernhard, Pochert, Nicole, Rouhi, Arefeh, Boccalatte, Francesco, Plati, Tiziana, Berg, Tobias, Sun, Su Ming, Mah, Sarah M., Mirkovic-Hösle, Milijana, Ruschmann, Jens, Muranyi, Andrew, Leierseder, Simon, Argiropoulos, Bob, Starczynowski, Daniel T., Karsan, Aly, Heuser, Michael, Hogge, Donna, Camargo, Fernando D., Engelhardt, Stefan, Döhner, Hartmut, Buske, Christian, Jongen-Lavrencic, Mojca, Naldini, Luigi, Humphries, R. Keith, and Kuchenbauer, Florian

Published
2015
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4. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1

Author

Schiroli, Giulia, Ferrari, Samuele, Conway, Anthony, Jacob, Aurelien, Capo, Valentina, Albano, Luisa, Plati, Tiziana, Castiello, Maria C., Sanvito, Francesca, Gennery, Andrew R., Bovolenta, Chiara, Palchaudhuri, Rahul, Scadden, David T., Holmes, Michael C., Villa, Anna, Sitia, Giovanni, Lombardo, Angelo, Genovese, Pietro, and Naldini, Luigi

Published
2017
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5. Lentiviral Hematopoietic Stem Cell Gene Therapy Benefits Metachromatic Leukodystrophy

Author

Biffi, Alessandra, Montini, Eugenio, Lorioli, Laura, Cesani, Martina, Fumagalli, Francesca, Plati, Tiziana, Baldoli, Cristina, Martino, Sabata, Calabria, Andrea, Canale, Sabrina, Benedicenti, Fabrizio, Vallanti, Giuliana, Biasco, Luca, Leo, Simone, Kabbara, Nabil, Zanetti, Gianluigi, Rizzo, William B., Mehta, Nalini A. L., Cicalese, Maria Pia, Casiraghi, Miriam, Boelens, Jaap J., Del Carro, Ubaldo, Dow, David J., Schmidt, Manfred, Assanelli, Andrea, Neduva, Victor, Di Serio, Clelia, Stupka, Elia, Gardner, Jason, von Kalle, Christof, Bordignon, Claudio, Ciceri, Fabio, Rovelli, Attilio, Roncarolo, Maria Grazia, Aiuti, Alessandro, Sessa, Maria, and Naldini, Luigi

Published
2013

6. Lentiviral vector common integration sites in preclinical models and a clinical trial reflect a benign integration bias and not oncogenic selection

Author

Biffi, Alessandra, Bartolomae, Cynthia C., Cesana, Daniela, Cartier, Natalie, Aubourg, Patrik, Ranzani, Marco, Cesani, Martina, Benedicenti, Fabrizio, Plati, Tiziana, Rubagotti, Enrico, Merella, Stefania, Capotondo, Alessia, Sgualdino, Jacopo, Zanetti, Gianluigi, von Kalle, Christof, Schmidt, Manfred, Naldini, Luigi, and Montini, Eugenio

Published
2011
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12. Interferon gene therapy reprograms the leukemia microenvironment inducing protective immunity to multiple tumor antigens.

Author

Escobar, Giulia, Barbarossa, Luigi, Barbiera, Giulia, Norelli, Margherita, Genua, Marco, Ranghetti, Anna, Plati, Tiziana, Camisa, Barbara, Brombin, Chiara, Cittaro, Davide, Annoni, Andrea, Bondanza, Attilio, Ostuni, Renato, Gentner, Bernhard, and Naldini, Luigi

Abstract

Immunotherapy is emerging as a new pillar of cancer treatment with potential to cure. However, many patients still fail to respond to these therapies. Among the underlying factors, an immunosuppressive tumor microenvironment (TME) plays a major role. Here we show that monocyte-mediated gene delivery of IFNα inhibits leukemia in a mouse model. IFN gene therapy counteracts leukemia-induced expansion of immunosuppressive myeloid cells and imposes an immunostimulatory program to the TME, as shown by bulk and single-cell transcriptome analyses. This reprogramming promotes T-cell priming and effector function against multiple surrogate tumor-specific antigens, inhibiting leukemia growth in our experimental model. Durable responses are observed in a fraction of mice and are further increased combining gene therapy with checkpoint blockers. Furthermore, IFN gene therapy strongly enhances anti-tumor activity of adoptively transferred T cells engineered with tumor-specific TCR or CAR, overcoming suppressive signals in the leukemia TME. These findings warrant further investigations on the potential development of our gene therapy strategy towards clinical testing. [ABSTRACT FROM AUTHOR]

Published
2018
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17. Development and maturation of invariant NKT cells in the presence of lysosomal engulfment.

Author

Plati, Tiziana, Visigalli, Ilaria, Capotondo, Alessia, Buono, Mario, Naldini, Luigi, Cosma, Maria Pia, and Biffi, Alessandra

Abstract

A defect in invariant NKT (iNKT) cell selection was hypothesized in lysosomal storage disorders (LSD). Accumulation of glycosphingolipids (GSL) in LSD could influence lipid loading and/or presentation causing entrapment of endogenous ligand(s) within storage bodies or competition of the selecting ligand(s) by stored lipids for CD1d binding. However, when we analyzed the iNKT cell compartment in newly tested LSD animal models that accumulate GSL, glycoaminoglycans or both, we observed a defective iNKT cell selection only in animals affected by multiple sulfatase deficiency, in which a generalized aberrant T-cell development, rather than a pure iNKT defect, was present. Mice with single lysosomal enzyme deficiencies had normal iNKT cell development. Thus, GSL/glycoaminoglycans storage and lysosomal engulfment are not sufficient for affecting iNKT cell development. Rather, lipid ligand(s) or storage compounds, which are affected in those LSD lacking mature iNKT cells, might indeed be relevant for iNKT cell selection. [ABSTRACT FROM AUTHOR]

Published
2009
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19. Preclinical modeling highlights the therapeutic potential of hematopoietic stem cell gene editing for correction of SCID-X1

Author

Giulia Schiroli, Anthony Conway, Samuele Ferrari, Michael C. Holmes, Luigi Naldini, Maria Carmina Castiello, Rahul Palchaudhuri, Anna Villa, Aurelien Jacob, Francesca Sanvito, Angelo Lombardo, Valentina Capo, Tiziana Plati, David T. Scadden, Chiara Bovolenta, Luisa Albano, Pietro Genovese, Giovanni Sitia, Andrew R. Gennery, Schiroli, Giulia, Ferrari, Samuele, Conway, Anthony, Jacob, Aurelien, Capo, Valentina, Albano, Luisa, Plati, Tiziana, Castiello, Maria C., Sanvito, Francesca, Gennery, Andrew R., Bovolenta, Chiara, Palchaudhuri, Rahul, Scadden, David T., Holmes, Michael C., Villa, Anna, Sitia, Giovanni, Lombardo, Angelo, Genovese, Pietro, and Naldini, Luigi

Subjects
0301 basic medicine, Mice, SCID, Computational biology, Biology, Bioinformatics, Mice, 03 medical and health sciences, Genome editing, medicine, Animals, CRISPR, Clustered Regularly Interspaced Short Palindromic Repeats, Progenitor cell, Gene Editing, Severe combined immunodeficiency, Cas9, Medicine (all), Hematopoietic stem cell, General Medicine, Hematopoietic Stem Cells, medicine.disease, Zinc finger nuclease, Haematopoiesis, 030104 developmental biology, medicine.anatomical_structure, Gene Targeting, Interleukin Receptor Common gamma Subunit
Abstract

Targeted genome editing in hematopoietic stem/progenitor cells (HSPCs) is an attractive strategy for treating immunohematological diseases. However, the limited efficiency of homology-directed editing in primitive HSPCs constrains the yield of corrected cells and might affect the feasibility and safety of clinical translation. These concerns need to be addressed in stringent preclinical models and overcome by developing more efficient editing methods. We generated a humanized X-linked severe combined immunodeficiency (SCID-X1) mouse model and evaluated the efficacy and safety of hematopoietic reconstitution from limited input of functional HSPCs, establishing thresholds for full correction upon different types of conditioning. Unexpectedly, conditioning before HSPC infusion was required to protect the mice from lymphoma developing when transplanting small numbers of progenitors. We then designed a one-size-fits-all IL2RG (interleukin-2 receptor common γ-chain) gene correction strategy and, using the same reagents suitable for correction of human HSPC, validated the edited human gene in the disease model in vivo, providing evidence of targeted gene editing in mouse HSPCs and demonstrating the functionality of the IL2RG-edited lymphoid progeny. Finally, we optimized editing reagents and protocol for human HSPCs and attained the threshold of IL2RG editing in long-term repopulating cells predicted to safely rescue the disease, using clinically relevant HSPC sources and highly specific zinc finger nucleases or CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein 9). Overall, our work establishes the rationale and guiding principles for clinical translation of SCID-X1 gene editing and provides a framework for developing gene correction for other diseases.

Published
2017

20. Brain conditioning is instrumental for successful microglia reconstitution following hematopoietic stem cell transplantation.

Author

Capotondo A, Milazzo R, Politi LS, Quattrini A, Palini A, Plati T, Merella S, Nonis A, di Serio C, Montini E, Naldini L, and Biffi A

Subjects
Analysis of Variance, Animals, Cell Differentiation physiology, Cell Movement physiology, Flow Cytometry, Green Fluorescent Proteins metabolism, In Situ Nick-End Labeling, Mice, Mice, Knockout, Hematopoietic Stem Cell Transplantation methods, Lysosomal Storage Diseases, Nervous System therapy, Microglia cytology, Transplantation Conditioning methods
Abstract

The recent hypothesis that postnatal microglia are maintained independently of circulating monocytes by local precursors that colonize the brain before birth has relevant implications for the treatment of various neurological diseases, including lysosomal storage disorders (LSDs), for which hematopoietic cell transplantation (HCT) is applied to repopulate the recipient myeloid compartment, including microglia, with cells expressing the defective functional hydrolase. By studying wild-type and LSD mice at diverse time-points after HCT, we showed the occurrence of a short-term wave of brain infiltration by a fraction of the transplanted hematopoietic progenitors, independently from the administration of a preparatory regimen and from the presence of a disease state in the brain. However, only the use of a conditioning regimen capable of ablating functionally defined brain-resident myeloid precursors allowed turnover of microglia with the donor, mediated by local proliferation of early immigrants rather than entrance of mature cells from the circulation.

Published
2012
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