Nuove strategie per generare DC tollerogeniche per l’immunoterapia specifica per Ag
- 5 Anni 2016/2021
- 1.258.986€ Totale Fondi
Gli obiettivi principali di questo progetto di ricerca sono generare cellule dendritiche tollerogeniche umane (tolDC) stabili ed efficaci adatte per approcci basati sull’infusione di tali cellule, svelare i meccanismi molecolari e cellulari che controllano la tolleranza immunitaria e identificare nuovi bersagli per controllare e indurre tolleranza. Abbiamo concentrato la nostra ricerca sulle cellule dendritiche secernenti IL-10: i nostri studi traslazionali hanno come finalità lo sviluppo di approcci innovativi per la modulazione di malattie immunitarie mediate dalle cellule T basati sull’infusione di cellule tolDC generate mediante trasferimento genico di IL-10 con vettori lentivirali. I nostri studi di base sono concentrati sulle cellule regolatorie che producono IL-10 e in particolare su una particolare classe di cellule, chiamate DC-10. Ci proponiamo di definire il ruolo delle cellule DC-10 nel promuovere/mantenere la tolleranza in condizioni sane e patologiche. Ci proponiamo anche di studiare il profilo genetico e epigenetico o delle cellule generate in vitro e isolate ex vivo, per comprendere meglio i meccanismi molecolari alla base della biologia delle cellule regolatorie. Il successo di questo progetto di ricerca ci aiuterà a ideare una terapia cellulare basata sulle cellule tolDC più sicura, eliminando la possibilità di reazioni avverse come l’aumento delle risposte autoimmuni e di preservare le proprietà tollerogeniche delle DC trasferite in vivo. Identificando profili genetici ed epigenetici che controllano le proprietà tollerogeniche delle cellule regolatorie, saremo anche in grado di sviluppare metodi nuovi/migliori per produrre cellule tolerogeniche per terapie cellulari finalizzare a ripristinare/indurre la tolleranza in vivo.
Pubblicazioni Scientifiche
- 2017-03-01 ANNALS OF TRANSLATIONAL MEDICINE
The discovery of HLA-G-bearing extracellular vesicles: new perspectives in HLA-G biology
- 2020-01-01 CELLULAR & MOLECULAR IMMUNOLOGY
Coexpression of CD163 and CD141 identifies human circulating IL-10-producing dendritic cells (DC-10)
- 2019-08-01 CELLULAR IMMUNOLOGY
Modulation of immune responses in lentiviral vector-mediated gene transfer
- 2020-01-01 CLINICAL & TRANSLATIONAL IMMUNOLOGY
Human-engineered Treg-like cells suppress FOXP3-deficient T cells but preserve adaptive immune responses in vivo
- 2024-03-01 CLINICAL IMMUNOLOGY
IL-10-producing regulatory cells impact on celiac disease evolution
- 2017-12-21 FRONTIERS IN IMMUNOLOGY
Monitoring t-cell responses in translational studies: optimization of Dye-Based Proliferation Assay for Evaluation of Antigen-specific responses
- 2018-02-22 FRONTIERS IN IMMUNOLOGY
Monitoring T-Cell Responses in Translational Studies: Optimization of Dye-Based Proliferation Assay for Evaluation of Antigen-Specific Responses (vol 8, 1870, 2017)
- 2018-02-15 FRONTIERS IN IMMUNOLOGY
Engineered T Regulatory Type 1 Cells for Clinical Application
- 2018-04-06 FRONTIERS IN IMMUNOLOGY
Interleukin-10-Producing DC-10 Is a Unique Tool to Promote Tolerance Via Antigen-Specific T Regulatory Type 1 Cells
- 2018-05-25 FRONTIERS IN IMMUNOLOGY
APVO210: A Bispecific Anti-CD86-IL-10 Fusion Protein (ADAPTIR™) to Induce Antigen-Specific T Regulatory Type 1 Cells
- 2020-06-30 FRONTIERS IN IMMUNOLOGY
Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer
- 2020-07-08 FRONTIERS IN IMMUNOLOGY
HLA-G Genotype/Expression/Disease Association Studies: Success, Hurdles, and Perspectives
- 2021-02-23 FRONTIERS IN IMMUNOLOGY
Regulatory Cell Therapy in Organ Transplantation: Achievements and Open Questions
- 2021-03-22 FRONTIERS IN IMMUNOLOGY
Generation of Powerful Human Tolerogenic Dendritic Cells by Lentiviral-Mediated IL-10 Gene Transfer (vol 11, 1260, 2020)
- 2021-10-01 FRONTIERS IN IMMUNOLOGY
Altered Frequency and Phenotype of HLA-G-Expressing DC-10 in Type 1 Diabetes Patients at Onset and in Subjects at Risk to Develop the Disease
- 2021-08-01 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Tolerogenic Dendritic Cell-Based Approaches in Autoimmunity
- 2023-05-23 INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
IL-10-Engineered Dendritic Cells Modulate Allogeneic CD8+ T Cell Responses
- 2018-01-01 JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
Peanut-specific type 1 regulatory T cells induced in vitro from allergic subjects are functionally impaired
- 2023-07-01 JOURNAL OF AUTOIMMUNITY
Tolerogenic IL-10-engineered dendritic cell-based therapy to restore antigen-specific tolerance in T cell mediated diseases
- 2019-10-01 JOURNAL OF CARDIOTHORACIC AND VASCULAR ANESTHESIA
A Systematic Review and International Web-Based Survey of Randomized Controlled Trials in the Perioperative and Critical Care Setting: Interventions Increasing Mortality
- 2018-08-06 NATURE COMMUNICATIONS
Myeloid apolipoprotein E controls dendritic cell antigen presentation and T cell activation
- 2020-01-01 TUMOR IMMUNOLOGY AND IMMUNOTHERAPY - CELLULAR METHODS, PT B
Protocol to assess the suppression of T-cell proliferation by human MDSC