Simona Manni
A5071908701- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Virus-based gene therapy research
- Epigenetics and DNA Methylation
- Hedgehog Signaling Pathway Studies
- Viral Infectious Diseases and Gene Expression in Insects
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- Hematopoietic Stem Cell Transplantation
- Immune cells in cancer
- Cancer-related Molecular Pathways
- Neuroblastoma Research and Treatments
- Chromatin Remodeling and Cancer
- Histone Deacetylase Inhibitors Research
- Bladder and Urothelial Cancer Treatments
- RNA Interference and Gene Delivery
- Cancer Research and Treatments
- Cancer, Lipids, and Metabolism
- Cancer, Stress, Anesthesia, and Immune Response
- Glioma Diagnosis and Treatment
- Sarcoma Diagnosis and Treatment
- Genomics and Chromatin Dynamics
Bambino Gesù Children's Hospital
2020-2025
Istituti di Ricovero e Cura a Carattere Scientifico
2021-2025
Sapienza University of Rome
2016-2020
Instytut Biologii Doświadczalnej im. Marcelego Nenckiego
2017
University of Parma
2015
Abstract Background Paediatric acute myeloid leukaemia (AML) is characterized by poor outcomes in patients with relapsed/refractory disease, despite the improvements intensive standard therapy. The leukaemic cells of paediatric AML show high expression CD123 antigen, and this finding provides biological basis to target chimeric antigen receptor (CAR). However, CAR.CD123 therapy hampered on-target off-tumour toxicity a long “vein-to-vein” time. Methods We developed an off-the-shelf product...
Abstract Chimeric antigen receptor T (CAR-T) cell therapy may achieve long-lasting remission in patients with B-cell malignancies not responding to conventional therapies. However, potentially severe and hard-to-manage side effects, including cytokine release syndrome (CRS), neurotoxicity macrophage activation syndrome, the lack of pathophysiological experimental models limit applicability development this form therapy. Here we present a comprehensive humanized mouse model, by which show...
Abstract Purpose: Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward disialoganglioside GD2 can represent potentially more effective treatment with reduced long-term Experimental Design: expression...
The prognosis of many patients with chemotherapy-refractory or multiply relapsed CD30+ non-Hodgkin Lymphoma (NHL) Hodgkin lymphoma (HL) still remains poor, and novel therapeutic approaches are warranted to address this unmet clinical need. In light consideration, we designed pre-clinically validated a Chimeric Antigen Receptor (CAR) construct characterized by anti-CD30 single-chain variable-fragment cassette, linked CD3ζ the signaling domains two costimulatory molecules, namely either...
T cells engineered with chimeric antigen receptor (CAR-T cells) are an effective treatment in patients relapsed/refractory B-cell precursor acute lymphoblastic leukemia or non-Hodgkin lymphoma. Despite the reported exciting clinical results, CAR-T cell approach needs efforts to improve safety profile, limiting occurrence of adverse events given this treatment. Besides most common side effects, such as cytokine release syndrome and cell–related encephalopathy syndrome, another potential issue...
Abstract SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with FDA-approved vismodegib, Hh inhibitor that targets transmembrane activator Smoothened (Smo), have shown rapid development drug resistance and relapse due to novel Smo mutations. Moreover, subset did not respond vismodegib because mutations were localized downstream Smo. Thus, targeting components now...
Highlights•Therapeutic doses of phenformin suppress Hedgehog-dependent tumor growth•Phenformin inhibits mGPD in cancer cells but does not affect complex I activity•Inhibition mimics and increases redox state/NADH content•Elevated NADH promotes Gli1/CtBP2 formation inhibition growthSummaryThe antidiabetic drug displays potent anticancer activity different tumors, its mechanism action remains elusive. Using Shh medulloblastoma as model, we show here that at clinically relevant concentrations,...
// Laura Di Magno 3 , Alessio Basile 1 Sonia Coni Simona Manni Giulia Sdruscia Davide D’Amico Antonucci Paola Infante Enrico De Smaele 2 Danilo Cucchi Elisabetta Ferretti Lucia Marcotullio 1, 3, 4 Isabella Screpanti Gianluca Canettieri Department of Molecular Medicine, Sapienza University Rome, 00161 Italy Experimental Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia, Roma, Pasteur, Fondazione Cenci-Bolognetti, Correspondence to: Canettieri, e-mail:...
Programmed cell death‐1 (PD‐1) signaling downregulates the T‐cell response, promoting an exhausted state in tumor‐infiltrating T cells, through mostly unveiled molecular mechanisms. Dynamin‐related protein‐1 (Drp1)‐dependent mitochondrial fission plays a crucial role sustaining motility, proliferation, survival, and glycolytic engagement. Interestingly, such processes are exactly those inhibited by PD‐1 cells. Here, we show that pos CD8 + cells infiltrating MC38 (murine...
The aberrant activation of hedgehog (HH) signaling is a leading cause the development medulloblastoma, pediatric tumor cerebellum. FDA‑approved HH inhibitor, Vismodegib, which targets transmembrane transducer SMO, has shown limited efficacy in patients with due to compensatory mechanisms that maintain an active HH‑GLI status. Thus, identification novel actionable mechanisms, directly affecting activity HH‑regulated GLI transcription factors important goal for these malignancies. In this...
Donor lymphocyte infusion (DLI) is employed to either treat or prevent relapse in patients with hematologic malignancies, as well accelerate recovery of adaptive immunity, after allogeneic hematopoietic stem cell transplantation (allo-HSCT). With the increased use DLI, there renewed interest development approaches able graft-versus-host disease (GvHD) reaction. In this study, we describe a novel and effective safety switch represented by truncated form human CD19 antigen (ΔCD19) used...
Chimeric antigen receptor T-cells (CAR T-cells) for the treatment of relapsing/refractory B-cell precursor acute lymphoblastic leukemia have led to exciting clinical results. However, CAR T-cell approaches revealed a potential risk CD19-/CAR+ leukemic relapse due inadvertent transduction cells. Background Methods We evaluated impact high percentage blast contamination in patient-derived starting material (SM) on drug product (DP) manufacturing. In vitro as well vivo models were employed...
Abstract Chimeric antigen receptor (CAR) T-cell therapy represents a revolutionary approach to induce long-lasting remission in patients with B-cell malignancies not responding conventional therapies. Nevertheless, possible severe side effects, including cytokine release syndrome (CRS), neurotoxicity and macrophage activation syndrome, whose management is still challenging, as well lack of pathophysiological experimental models investigate novel interventions, limit the widespread use this...
Sarcomas are rare, mesenchymal tumors, representing about 10–15% of all childhood cancers. GD2 is a suitable target for chimeric antigen receptor (CAR) T-cell therapy due to its overexpression in several solid tumors. In this preclinical study, we investigated the potential use iCasp9.2A.GD2.CAR-CD28.4–1BBζ (CAR.GD2) T-cells as treatment option patients who have GD2-positive sarcomas and sought identify factors shaping hostile tumor microenvironment setting. expression was evaluated by...
<p>Supplemental Figure 12. DAOY-GFP tumor bearing-mice treated with Tazemetostat to evaluate GD2 upregulation in vivo.</p>
<p>Supplemental Figure 5. Real-Time killing assay of CAR.GD2 T-cells vs DAOY-GFP cell line.</p>
<div>AbstractPurpose:<p>Medulloblastoma (MB), the most common childhood malignant brain tumor, has a poor prognosis in about 30% of patients. The current standard care, which includes surgery, radiation, and chemotherapy, is often responsible for cognitive, neurologic, endocrine side effects. We investigated whether chimeric antigen receptor (CAR) T cells directed toward disialoganglioside GD2 can represent potentially more effective treatment with reduced long-term...
<p>Supplemental Figure 6. CAR.GD2 T-cells spare the elimination of MB cells with a dim expression GD2.</p>
<p>Supplemental Figure 14. Orthotopic PDX mouse model of human MED-411 FH mCherry/Luc cell line to evaluate anti-tumor activity CAR.GD2 T-cells.</p>
<p>Supplemental Video 2. IncuCyte® live-cell System video of Cytotoxic activity NT or CAR.GD2 T-cells vs DAOY-GFP-FF-Luc cell line. The shows 84 hours tumor growth (DAOY line) with only (A) and cells co-cultured (B) (C).</p>
<p>Supplemental Figure 8. Tazemetostat did not modulate GD2 expression in normal cells.</p>
<p>Supplemental Figure 17. Evaluation of the NT T-cell infiltration in MB xenograft mouse model.</p>
<p>Supplemental Video 2. IncuCyte® live-cell System video of Cytotoxic activity NT or CAR.GD2 T-cells vs DAOY-GFP-FF-Luc cell line. The shows 84 hours tumor growth (DAOY line) with only (A) and cells co-cultured (B) (C).</p>