A5060869891- CAR-T cell therapy research
- Monoclonal and Polyclonal Antibodies Research
- Biosimilars and Bioanalytical Methods
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Cancer Research and Treatments
- Acute Ischemic Stroke Management
- Glioma Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Enzyme function and inhibition
- Cerebrovascular and Carotid Artery Diseases
- Radiopharmaceutical Chemistry and Applications
- Synthesis and Catalytic Reactions
- Immune Cell Function and Interaction
- Nonmelanoma Skin Cancer Studies
- Cerebrovascular and genetic disorders
- Intracranial Aneurysms: Treatment and Complications
- Cell Adhesion Molecules Research
- Cancer, Hypoxia, and Metabolism
- Glycosylation and Glycoproteins Research
- Chemokine receptors and signaling
- Traumatic Brain Injury and Neurovascular Disturbances
- Phenothiazines and Benzothiazines Synthesis and Activities
- Moyamoya disease diagnosis and treatment
- Nanoplatforms for cancer theranostics
Philochem (Switzerland)
2020-2025
Philogen (Italy)
2022-2025
Ospedali Riuniti Umberto I
2022-2023
University of Macerata
2023
Ospedale San Paolo
2023
IRCCS San Camillo Hospital
2022
Marche Polytechnic University
2022
ETH Zurich
2019-2020
Sapienza University of Rome
2006-2014
Fondazione IRCCS Istituto Neurologico Carlo Besta
2014
Immunocytokines display promising antitumor activity in orthotopic mouse models of glioma and patients with glioblastoma.
Glioblastoma is the most aggressive primary brain tumor with an unmet need for more effective therapies. Here, we investigated combination therapies based on L19TNF, antibody-cytokine fusion protein necrosis factor that selectively localizes to cancer neovasculature. Using immunocompetent orthotopic glioma mouse models, identified strong anti-glioma activity of L19TNF in alkylating agent CCNU, which cured majority tumor-bearing mice, whereas monotherapies only had limited efficacy. In situ...
We describe the cloning and characterization of a novel fusion protein (termed L19‐mIL12), consisting murine interleukin‐12 in single‐chain format, sequentially fused to L19 antibody tandem diabody format. The bound avidly cognate antigen (the alternatively spliced EDB domain fibronectin), retained activity parental cytokine was able selectively localize tumors vivo , as shown by quantitative biodistribution analysis. L19‐mIL12 exhibited potent antitumor immunocompetent mice bearing CT26...
Background and Purpose: Observational studies have suggested a link between fibromuscular dysplasia spontaneous cervical artery dissection (sCeAD). However, whether patients with coexistence of the two conditions distinctive clinical characteristics has not been extensively investigated. Methods: In cohort consecutive first-ever sCeAD, enrolled in setting multicenter IPSYS CeAD study (Italian Project on Stroke Young Adults Cervical Artery Dissection) January 2000 June 2019, we compared...
In this study, we describe the generation of a fully human monoclonal antibody (named '7NP2') targeting fibroblast activation protein (FAP), an antigen expressed in microenvironment different types solid neoplasms.7NP2 was isolated from synthetic phage display library and improved by one round mutagenesis-based affinity maturation. The tumor recognition properties were validated immunofluorescence procedures performed on cancer biopsies patients. A fusion consisting 7NP2 linked to...
Abstract Background Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and deadly type cancer, with an extremely low five-year overall survival rate. To date, current treatment options primarily involve various chemotherapies, which often prove ineffective are associated substantial toxicity. Furthermore, immunotherapies utilizing checkpoint inhibitors have shown limited efficacy in this context, highlighting urgent need for novel therapeutic strategies. This study...
Abstract T-cell-engaging bispecific antibodies (TCBs) are an expanding modality in immunotherapy, designed to redirect T-cell cytotoxicity toward tumor cells by cross-linking them with tumor-associated antigens1. While TCBs have shown significant efficacy hematological malignancies, their success solid tumors remains limited2. This is likely due multiple factors, including the low number of T microenvironment and presence immunosuppressive conditions that hinder activity3, 4. In this study,...
Prostate cancer is the second deadliest tumor in men globally, despite advent of novel drugs. Therapeutic modalities targeting Specific Membrane Antigen (PSMA) have provided benefit to patients but suffer from on-target off-tumor liabilities responsible for side effects observed clinical practice. These are a result expression PSMA healthy tissues, such as salivary glands, lacrimal intestine, and kidneys. Innovative ligands against better prostate targets therefore needed. Here, we present...
Background The administration of recombinant interleukin 2 (IL-2) in oncology is frequently hampered by dose-limiting toxicities, including potentially lethal vascular leak syndrome. Antibody-IL-2 fusion proteins capable preferential tumor localization have shown encouraging signs activity clinical trials; however, they typically cause side effects shortly after intravenous administration, which may limit escalation to curative doses. There an urgent need engineer IL-2 products with...
Emergency Clinical Pathways (ECP) for stroke have never been tested in randomized controlled trials (RCTs).To evaluate the effectiveness of an ECP patients Latium (Italy) emergency system.cluster-RCT designed to compare patient referrals by Medical Service (EMS) and Room (ER) health professionals trained ECP, with those non-trained EMS ER controls. Primary outcome measure was proportion eligible (aged </= 80 symptom onset 6 hours) referred a unit (SU). Intention treat (ITT) per-protocol (PP)...
Anti-PD-1 antibodies have revolutionized cancer immunotherapy due to their ability induce long-lasting complete remissions in a proportion of patients. Current research efforts are attempting identify biomarkers and suitable combination partners predict or further improve the activity immune checkpoint inhibitors. Antibody-cytokine fusions class pharmaceuticals that showed potential boost anticancer properties other immunotherapies. Extradomain A-fibronectin (EDA-FN), which is expressed most...
<h3>Background and purpose</h3> CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts leukoencephalopathy) is a rare genetic disease caused by <i>NOTCH3</i> gene mutations. A dysfunction in vasoreactivity has been proposed as an early event the pathogenesis of disease. The aim this study was to verify whether endothelium dependent and/or independent function altered patients respect controls. <h3>Methods</h3> Vasoreactivity studied non-invasive pletismographic method 49...
Interferon-gamma (IFNγ) is one of the central cytokines produced by innate and adaptive immune systems. IFNγ directly favors tumor growth control enhancing immunogenicity cells, induces IP-10 secretion facilitating (CXCR3+) cell infiltration, can prime macrophages to an M1-like phenotype inducing proinflammatory cytokine release. We had previously reported that targeted delivery neoplastic lesions may be limited trapping IFNγ-based products cognate receptors found in different organs. Here...
Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a rare autosomal dominant disorder caused by NOTCH3 mutations, is characterized vascular smooth muscle endothelial cells abnormalities, altered vasoreactivity, recurrent lacunar infarcts. Vasomotor function may represent key factor for disease progression. Tetrahydrobiopterin, essential cofactor nitric oxide synthesis in cells, ameliorates function. We assessed whether supplementation...
There are no effective treatment options for most patients with metastatic colorectal cancer (mCRC). mCRC remains a leading cause of tumor-related death, five-year survival rate only 15%, highlighting the urgent need novel pharmacological products. Current standard drugs based on cytotoxic chemotherapy, VEGF inhibitors, EGFR antibodies, and multikinase inhibitors. The antibody-based delivery pro-inflammatory cytokines provides promising differentiated strategy to improve outcome patients....
Transient ischemic attacks (TIAs) bear a presumed high risk of early recurrence stroke. Data in the literature, however, are inconsistent, as rates range from 9.5 to 20%, at 90 days.The study was designed determine stroke after TIA.94 consecutive patients referred Stroke Unit for TIA or minor stroke, within 24 h symptom onset, were recruited. Eleven 94 (12%, 95% CI: 7-20%) had relapse days. The consisted 9 (10%, 5-17%), 2 subjects (1%, 0-8%). More than quarter relapses occurred 1 week first...
Programmed cell death protein 1 (PD-1) is an immunoregulatory target which recognized by different monoclonal antibodies, approved for the therapy of multiple types cancer. Different anti-PD-1 antibodies display therapeutic properties and there a pharmaceutical interest to generate characterize novel antibodies. We screened human antibody phage libraries epitopes on PD-1 surface we discovered unique previously undescribed binding specificity (termed D12) from new library AMG). The featured...
Abstract Small molecule–drug conjugates (SMDCs) represent an alternative to conventional antitumor chemotherapeutic agents, with the potential improve therapeutic window of cytotoxic payloads through active delivery at site disease. In this article, we describe novel combination therapies consisting anti-carbonic anhydrase IX SMDCs combined different immunomodulatory products. The effect was potentiated by PD-1 blockade and tumor-homing antibody–cytokine fusions in mouse models renal cell...
The delivery of specific cytokine payloads to a neoplastic environment employing antibodies able selectively accumulate at the tumor site represents an attractive strategy stimulate immune response cancer. Whilst conventional antibody-cytokine fusions based on single payload have shown potent anticancer activity, concomitant two may further improve therapeutic outcome as system typically adopts multiple signals reinforce antitumor strategy. We here describe potency-matched dual-cytokine...