Search results for " Antibody"

Cyclic hantavirus epidemics in humans--predicted by rodent host dynamics.

2009

Wildlife-originated zoonotic diseases are a major contributor to emerging infectious diseases. Hantaviruses cause thousands of human disease cases annually worldwide, and understanding and predicting human hantavirus epidemics still poses unsolved challenges. Here we studied the three-level relationships between the human disease nephropathia epidemica (NE), its etiological agent Puumala hantavirus (PUUV) and the rodent host of the virus, the bank vole (Myodes glareolus). A large and long-term data set (14 years, 2583 human NE cases and 4751 trapped bank voles) indicates that the number of human infections shows both seasonal and multi-annual fluctuations, is influenced by the phase of vole…

Antibodies against Lewis antigens inhibit the binding of human norovirus GII.4 virus-like particles to saliva but not to intestinal Caco-2 cells.

2016

BACKGROUND: Human noroviruses (NoVs) are the main cause of gastroenteritis worldwide. The most commonly detected NoV strains belong to the genetically diverse GII.4 genotype, with new pandemic variants emerging periodically. Despite extensive efforts, NoV investigation has been hampered by the lack of an effective in vitro cell culture system. However, NoV-derived recombinant virus-like particles (VLPs) resembling empty capsids are good surrogates for analysing NoV antigenicity and virus-ligand interactions. NoV VLPs have been reported to bind to histo-blood group antigens (HBGAs). We have analysed the ability of NoV VLPs derived from GI.1 genotype and from three GII.4 genotype variants, GI…

The CD68+/H-ferritin+ cells colonize the lymph nodes of the patients with adult onset Still's disease and are associated with increased extracellular…

2015

Summary In this work, we aimed to evaluate the levels of ferritin enriched in H subunits (H-ferritin) and ferritin enriched in L subunits (L-ferritin) and the cells expressing these two molecules in the lymph node (LN) biopsies obtained from adult-onset Still's disease (AOSD) patients, and the possible correlation among these data and the severity of the disease. Ten patients with AOSD underwent LN biopsy. All the samples were stained by immunofluorescence. A statistical analysis was performed to estimate the possible correlation among both H-ferritin and L-ferritin tissue expression and the clinical picture of the disease. Furthermore, the same analysis was performed to evaluate the possib…

Preliminary results from a phase I study of GBR 1302, a bispecific antibody T-cell engager, in HER2 positive cancers

2018

CD36-fibrin interaction propagates FXI-dependent thrombin generation of human platelets.

2019

Thrombin converts fibrinogen to fibrin and activates blood and vascular cells in thrombo-inflammatory diseases. Platelets are amplifiers of thrombin formation when activated by leukocyte- and vascular cell-derived thrombin. CD36 on platelets acts as sensitizer for molecules with damage-associated molecular patterns, thereby increasing platelet reactivity. Here, we investigated the role of CD36 in thrombin-generation on human platelets, including selected patients with advanced chronic kidney disease (CKD). Platelets deficient in CD36 or blocked by anti-CD36 antibody FA6.152 showed impaired thrombin generation triggered by thrombin in calibrated automated thrombography. Using platelets with …

A phase I study of the bispecific antibody T-cell engager GBR 1302 in subjects with HER2-positive cancers.

2017

TPS3091 Background: GBR 1302, a bispecific antibody based on Glenmark’s BEAT platform, is designed to recruit cytotoxic T-cells (independent of their specificity) to HER2-positive cancer cells where they are activated by the CD3e-specific domain of the molecule. Preclinically, GBR 1302 has demonstrated potent killing of HER2-positive human cancer cells (HER2 3+ or 2+ by IHC HercepTest), as well as growth suppression of the trastuzumab-resistant cell line JIMT-1. In contrast, the GBR 1302 concentration required to kill primary cardiomyocytes with normal HER2 levels was up to 1000 times greater than the concentration needed to kill HER2 3+ tumor cell lines. This study will determine safety a…

Extracellular Vesicles Shed by Melanoma Cells Contain a Modified Form of H1.0 Linker Histone and H1.0 mRNA-binding Proteins

2016

Extracellular vesicles (EVs) are shed in the extracellular environment by both prokaryotes and eukaryotes. Although produced from both normal and cancer cells, malignant cells release a much higher amount of EVs, which also contain tumor-specific proteins and RNAs. We previously found that G26/24 oligodendroglioma cells shed EVs that contain the pro-apoptotic factors FasL and TRAIL1-2. Interestingly, G26/24 release, via EVs, extracellular matrix remodelling proteases3, and H1° histone protein4, and mRNA. To shed further light on the role of EVs in discarding proteins and mRNAs otherwise able to counteract proliferative signals, we studied a melanoma cell line (A375). We found that also thes…

A receptor-antibody hybrid hampering MET-driven metastatic spread

2021

AbstractBackgroundThe receptor encoded by the MET oncogene and its ligand Hepatocyte Growth Factor (HGF) are at the core of the invasive-metastatic behavior. In a number of instances genetic alterations result in ligand-independent onset of malignancy (METaddiction). More frequently, ligand stimulation of wild-type MET contributes to progression toward metastasis (METexpedience). Thus, while MET inhibitors alone are effective in the first case, combination therapy with ligand inhibitors is required in the second condition.MethodsIn this paper, we generated hybrid molecules gathering HGF and MET inhibitory properties. This has been achieved by ‘head-to-tail’ or ‘tail-to-head’ fusion of a sin…

Dual Constant Domain-Fab: A novel strategy to improve half-life and potency of a Met therapeutic antibody

2016

The kinase receptor encoded by the Met oncogene is a sensible target for cancer therapy. The chimeric monovalent Fab fragment of the DN30 monoclonal antibody (MvDN30) has an odd mechanism of action, based on cell surface removal of Met via activation of specific plasma membrane proteases. However, the short half-life of the Fab, due to its low molecular weight, is a severe limitation for the deployment in therapy. This issue was addressed by increasing the Fab molecular weight above the glomerular filtration threshold through the duplication of the constant domains, in tandem (DCD-1) or reciprocally swapped (DCD-2). The two newly engineered molecules showed biochemical properties comparable…

Monoclonal Antibodies, Bispecific Antibodies and Antibody-Drug Conjugates in Oncohematology

2020

Background: The therapeutic outcomes and the prognosis of patients with various hematologic malignancies are not always ideal with the current standard of care. Objective: The aim of this study is to analyze the results of the use of monoclonal antibodies, bispecific antibodies and antibody-drug conjugates for the therapy of malignant hemopathies. Methods: A mini-review was achieved using the articles published in Web of Science and PubMed between January 2017 and January 2020 and the new patents were made in this field. Results: Naked monoclonal antibodies have improved the therapeutic results obtained with standard of care, but they also have side effects and the use of some of them can …