10 results on '"Luca Cesana"'
Search Results
2. Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
- Author
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Michela Comi, Giada Amodio, Laura Passeri, Marta Fortunato, Francesca Romana Santoni de Sio, Grazia Andolfi, Anna Kajaste-Rudnitski, Fabio Russo, Luca Cesana, and Silvia Gregori
- Subjects
dendritic cells ,IL-10 ,cell therapy ,immune tolerance ,allogeneic transplantation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DCIL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation.
- Published
- 2020
- Full Text
- View/download PDF
3. Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases
- Author
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Laura Passeri, Grazia Andolfi, Virginia Bassi, Fabio Russo, Giorgia Giacomini, Cecilia Laudisa, Ilaria Marrocco, Luca Cesana, Marina Di Stefano, Lorella Fanti, Paola Sgaramella, Serena Vitale, Chiara Ziparo, Renata Auricchio, Graziano Barera, Giovanni Di Nardo, Riccardo Troncone, Carmen Gianfrani, Andrea Annoni, Laura Passerini, and Silvia Gregori
- Subjects
immune tolerance ,tr1 cells ,type 1 diabetes ,celiac disease ,dendritic cells ,il-10 ,Immunology ,Immunology and Allergy - Published
- 2023
4. Normative data for Lezak’s Tinkertoy test in healthy Italian adults [version 1; referees: 2 approved with reservations]
- Author
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Franca Crippa, Luca Cesana, and Roberta Daini
- Subjects
Research Article ,Articles ,Neurorehabilitation & CNS Trauma ,Sensory Systems ,executive functions ,brain lesions ,neuropsychological assessment ,confounding effects - Abstract
The Tinkertoy test is a tool for the neuropsychological assessment of executive functions and a predictor of employability. Originally a children’s toy comprising pieces to assemble freely, the TinkerToy Test examines organizational abilities, planning, and response flexibility. It allows subjects to use their own initiative and does not force them to choose from a series of predetermined alternatives. Tinkertoy test normative values were collected from 256 neurologically healthy Italian subjects. Multivariable analysis showed sex and education to have significant confounding effects. Adjusted and inferential cut-off points were determined and converted into equivalent scores, applying a distribution-free technique.
- Published
- 2016
- Full Text
- View/download PDF
5. Corrigendum: Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
- Author
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Giada Amodio, Fabio Russo, Francesca Romana Santoni de Sio, Silvia Gregori, Michela Comi, Grazia Andolfi, Anna Kajaste-Rudnitski, Luca Cesana, Laura Passeri, and Marta Fortunato
- Subjects
lcsh:Immunologic diseases. Allergy ,immune tolerance ,Allogeneic transplantation ,Immunology ,Gene transfer ,Biology ,allogeneic transplantation ,Immune tolerance ,Cell therapy ,Interleukin 10 ,IL-10 ,Cancer research ,Immunology and Allergy ,dendritic cells ,cell therapy ,lcsh:RC581-607 - Published
- 2021
6. Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
- Author
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Fabio Russo, Giada Amodio, Anna Kajaste-Rudnitski, Grazia Andolfi, Michela Comi, Marta Fortunato, Francesca Romana Santoni de Sio, Laura Passeri, Silvia Gregori, and Luca Cesana
- Subjects
lcsh:Immunologic diseases. Allergy ,Adoptive cell transfer ,immune tolerance ,T-Lymphocytes ,T cell ,Genetic Vectors ,Immunology ,Gene Expression ,Biology ,Monocytes ,Immunophenotyping ,Immune tolerance ,Viral vector ,Cell therapy ,Mice ,Immune system ,Transduction, Genetic ,medicine ,Animals ,Humans ,Immunology and Allergy ,dendritic cells ,Original Research ,Lentivirus ,Correction ,Interleukin-10 ,Cell biology ,allogeneic transplantation ,Interleukin 10 ,medicine.anatomical_structure ,Humanized mouse ,IL-10 ,Female ,cell therapy ,lcsh:RC581-607 - Abstract
The prominent role of dendritic cells (DC) in promoting tolerance and the development of methods to generate clinical grade products allowed the clinical application of tolerogenic DC (tolDC)-based therapies for controlling unwanted immune responses. We established an efficient method to generate tolerogenic human DC, producing supra-physiological levels of IL-10, by genetically engineering monocyte-derived DC with a bidirectional Lentiviral Vector (bdLV) encoding for IL-10 and a marker gene. DCIL−10 are mature DC, modulate T cell responses, promote T regulatory cells, and are phenotypically and functionally stable upon stimulation. Adoptive transfer of human DCIL−10 in a humanized mouse model dampens allogeneic T cell recall responses, while murine DCIL−10 delays acute graft-vs.-host disease in mice. Our report outlines an efficient method to transduce human myeloid cells with large-size LV and shows that stable over-expression of IL-10 generates an effective cell product for future clinical applications in the contest of allogeneic transplantation.
- Published
- 2020
7. AKT1 and BRAF mutations in pediatric aggressive fibromatosis
- Author
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Silvana Pilotti, Nicholas Paielli, Antonino Belfiore, Maura Massimino, Federica Perrone, Alessandro Gronchi, Cristina Meazza, Andrea Ferrari, Adele Busico, Stefano Chiaravalli, Giulio Settanni, Luca Cesana, and Chiara Colombo
- Subjects
0301 basic medicine ,Male ,Proto-Oncogene Proteins B-raf ,Cancer Research ,CTNNB1, TP53 ,Adolescent ,Adenomatous polyposis coli ,VEGF receptors ,pediatric aggressive fibromatosis ,AKT1 ,Gene mutation ,Genetic profile ,BRAF ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Genetic Predisposition to Disease ,Child ,beta Catenin ,Original Research ,Cancer Biology ,Sanger sequencing ,biology ,High-Throughput Nucleotide Sequencing ,Infant ,medicine.disease ,Prognosis ,Fibromatosis, Aggressive ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Child, Preschool ,Aggressive fibromatosis ,Mutation ,biology.protein ,Cancer research ,symbols ,Female ,Tumor Suppressor Protein p53 ,Proto-Oncogene Proteins c-akt - Abstract
Aside from the CTNNB1 and adenomatous polyposis coli (APC) mutations, the genetic profile of pediatric aggressive fibromatosis (AF) has remained poorly characterized. The aim of this study was to shed more light on the mutational spectrum of pediatric AF, comparing it with its adult counterpart, with a view to identifying biomarkers for use as prognostic factors or new potential therapeutic targets. CTNNB1,APC,AKT1,BRAF TP53, and RET Sanger sequencing and next‐generation sequencing (NGS) with the 50‐gene Ion AmpliSeq Cancer Hotspot Panel v2 were performed on formalin‐fixed samples from 28 pediatric and 33 adult AFs. The prognostic value of CTNNB1,AKT1, and BRAF mutations in pediatric AF patients was investigated. Recurrence‐free survival (RFS) curves were estimated with the Kaplan–Meier method and statistical comparisons were drawn using the log‐rank test. In addition to the CTNNB1 mutation (64%), pediatric AF showed AKT1 (31%), BRAF (19%), and TP53 (9%) mutations, whereas only the CTNNB1 mutation was found in adult AF. The polymorphism Q472H VEGFR was identified in both pediatric (56%) and adult (40%) AF. Our results indicate that the mutational spectrum of pediatric AF is more complex than that of adult AF, with multiple gene mutations involving not only CTNNB1 but also AKT1 and BRAF. This intriguing finding may have clinical implications and warrants further investigations.
- Published
- 2016
8. IL-10-Engineered Human CD4
- Author
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Grazia, Locafaro, Grazia, Andolfi, Fabio, Russo, Luca, Cesana, Antonello, Spinelli, Barbara, Camisa, Fabio, Ciceri, Angelo, Lombardo, Attilio, Bondanza, Maria Grazia, Roncarolo, and Silvia, Gregori
- Subjects
CD4-Positive T-Lymphocytes ,surgical procedures, operative ,tolerance ,immune system diseases ,Leukemia, Myeloid ,Leukocytes, Mononuclear ,Humans ,Original Article ,immunotherapy ,gene transfer ,Models, Biological ,T-Lymphocytes, Regulatory ,Interleukin-10 - Abstract
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4+ T cells into T regulatory type 1 (Tr1)-like (CD4IL-10) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models. In the present study, we show that CD4IL-10 cells mediate anti-leukemic effects in vitro and in vivo in a human leukocyte antigen (HLA) class I-dependent but antigen-independent manner. The cytotoxicity mediated by CD4IL-10 cells is granzyme B (GzB) dependent, is specific for CD13+ target cells, and requires CD54 and CD112 expression on primary leukemic target blasts. CD4IL-10 cells adoptively transferred in humanized mouse models directly mediate anti-tumor and anti-leukemic effects. In addition, when co-transferred with peripheral blood mononuclear cells (PBMCs), CD4IL-10 cells contribute to the GvL activity but suppress xenoGvHD mediated by the PBMCs. These findings provide for the first time a strong rationale for CD4IL-10 cell immunotherapy to prevent GvHD and promote GvL in allo-HSCT for myeloid malignancies., Graphical Abstract, Tr1 cells are generated by overexpressing IL-10 in CD4+ T cells (CD4IL-10). In this issue of Molecular Therapy, Locafaro et al. (2017) show that CD4IL-10 cells kill myeloid leukemia in an HLA class I-dependent mechanism, mediate anti-tumor and anti-leukemic effects, and contribute to GvL while preventing GvHD in humanized mice.
- Published
- 2017
9. IL-10-Engineered Human CD4+ Tr1 Cells Eliminate Myeloid Leukemia in an HLA Class I-Dependent Mechanism
- Author
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Fabio Ciceri, Antonello E. Spinelli, Fabio Russo, Barbara Camisa, Angelo Lombardo, Grazia Andolfi, Maria Grazia Roncarolo, Luca Cesana, Silvia Gregori, Attilio Bondanza, Grazia Locafaro, Locafaro, Grazia, Andolfi, Grazia, Russo, Fabio, Cesana, Luca, Spinelli, Antonello, Camisa, Barbara, Ciceri, Fabio, Lombardo, ANGELO LEONE, Bondanza, Attilio, Roncarolo, MARIA GRAZIA, and Gregori, Silvia
- Subjects
0301 basic medicine ,Myeloid ,medicine.medical_treatment ,Hematopoietic stem cell transplantation ,Human leukocyte antigen ,Biology ,03 medical and health sciences ,Genetic ,immune system diseases ,Drug Discovery ,Genetics ,medicine ,Gene transfer ,Molecular Biology ,Pharmacology ,Drug Discovery3003 Pharmaceutical Science ,Myeloid leukemia ,Immunotherapy ,Granzyme B ,Interleukin 10 ,surgical procedures, operative ,030104 developmental biology ,medicine.anatomical_structure ,Immunology ,Humanized mouse ,Molecular Medicine ,Tolerance - Abstract
T regulatory cells (Tregs) play a key role in modulating T cell responses. Clinical trials showed that Tregs modulate graft-versus-host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, their ability to mediate anti-leukemic activity (graft-versus-leukemia [GvL]) is largely unknown. Enforced interleukin-10 (IL-10) expression converts human CD4+ T cells into T regulatory type 1 (Tr1)-like (CD4IL-10) cells that suppress effector T cells in vitro and xenoGvHD in humanized mouse models. In the present study, we show that CD4IL-10 cells mediate anti-leukemic effects in vitro and in vivo in a human leukocyte antigen (HLA) class I-dependent but antigen-independent manner. The cytotoxicity mediated by CD4IL-10 cells is granzyme B (GzB) dependent, is specific for CD13+ target cells, and requires CD54 and CD112 expression on primary leukemic target blasts. CD4IL-10 cells adoptively transferred in humanized mouse models directly mediate anti-tumor and anti-leukemic effects. In addition, when co-transferred with peripheral blood mononuclear cells (PBMCs), CD4IL-10 cells contribute to the GvL activity but suppress xenoGvHD mediated by the PBMCs. These findings provide for the first time a strong rationale for CD4IL-10 cell immunotherapy to prevent GvHD and promote GvL in allo-HSCT for myeloid malignancies. Tr1 cells are generated by overexpressing IL-10 in CD4+ T cells (CD4IL-10). In this issue of Molecular Therapy, Locafaro et al. (2017) show that CD4IL-10 cells kill myeloid leukemia in an HLA class I-dependent mechanism, mediate anti-tumor and anti-leukemic effects, and contribute to GvL while preventing GvHD in humanized mice.
- Published
- 2017
10. Normative data for Lezak’s Tinkertoy test in healthy Italian adults
- Author
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F Crippa, Roberta Daini, and Luca Cesana
- Subjects
General Immunology and Microbiology ,medicine.diagnostic_test ,business.industry ,05 social sciences ,Flexibility (personality) ,General Medicine ,Employability ,Plant biology ,Executive functions ,050105 experimental psychology ,General Biochemistry, Genetics and Molecular Biology ,Test (assessment) ,03 medical and health sciences ,0302 clinical medicine ,Normative ,Medicine ,0501 psychology and cognitive sciences ,Neuropsychological assessment ,General Pharmacology, Toxicology and Pharmaceutics ,business ,Neuroscience ,030217 neurology & neurosurgery ,Clinical psychology - Abstract
The Tinkertoy test is a tool for the neuropsychological assessment of executive functions and a predictor of employability. Originally a children’s toy comprising pieces to assemble freely, the TinkerToy Test examines organizational abilities, planning, and response flexibility. It allows subjects to use their own initiative and does not force them to choose from a series of predetermined alternatives. Tinkertoy test normative values were collected from 256 neurologically healthy Italian subjects. Multivariable analysis showed sex and education to have significant confounding effects. Adjusted and inferential cut-off points were determined and converted into equivalent scores, applying a distribution-free technique.
- Published
- 2016
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