89 research outputs found
The promise of anti-ErbB3 monoclonals as new cancer therapeutics
No full textIn the last 3-5 years strong evidence has been gathered demonstrating ErbB3 as a key node for the progression of several cancer types. From the mechanistic standpoint the intracellular region of this receptor is rich of tyrosine residues that, upon phosphorylation, become high affinity binding sites for PI3K and other proteins involved in signal transduction. The involvement of ErbB3 occurs at different levels, most likely as a consequence of its promiscuity in the interaction with other RTKs of the same or other families. Several efforts are therefore being put in the development of antibodies that target this receptor either singly or in combination with other synergizing receptors. Some of these compounds have already entered clinical development. Although clinical proof-of-concept has not yet been achieved, this is likely to occur soon and will further accelerate the inclusion of anti-ErbB3 monoclonals in the repertoire of anticancer agents for more effective combination therapy. In this paper we review the wealth of anti-ErbB3 antibodies under development and compare their properties and potential to become marketed drugs
Study of the light response of an arch-shaped scintillator with direct coupling to a Silicon Photomultiplier readout
No full textWe report about a study of the light response of a solid polystyrene-based scintillator with an arch shaped geometry, directly coupled to Silicon Photo Multiplier sensors for the light readout. This geometry is relevant for the design of a novel borehole detector for "muography" applications in Civil Engineering, Geology or Archaeology. The scintillator response has been investigated using a dedicated experimental set-up based on the detection of cosmic ray muons. Configurations that use reflecting and diffusive materials have been tested, as well as configurations with a cover specifically designed to enclose and protect the scintillator. The results found a good compromise between the light response and an easy solution for the detector assembly
A novel cylindrical detector for borehole muon radiography
No full textMuography (or muon radiography) is a recent imaging methodology that uses cosmic muons to investigate the mass distribution in large objects, such as volcanoes or mines, or to detect the presence of cavities in the subsoil or within buildings such as the pyramids. In recent years detectors with different geometries, sizes and technologies have been developed. In particular detectors with reduced size, that can be inserted in a borehole, are of particular interest in geophysical applications. We have developed, and patented, an innovative detector for well applications consisting of plastic scintillators with arc shape and rectangular section bars. Good spatial resolution was achieved with a reasonable number of channels. Detailed simulations based on Monte Carlo methods have shown excellent performance in cavity detection. Preliminary results of a prototype show good performance in terms of the number of photoelectrons produced by cosmic muons and track reconstruction
Muon Radiography Investigations in Boreholes with a Newly Designed Cylindrical Detector
No full textMuons are constantly produced in cosmic-rays and reach the Earth surface with a flux of about 160 particles per second per square meter. The abundance of muons with respect to other cosmic particles and their capability to cross dense materials with low absorption rate allow them to be exploited for large scale geological or human-made object imaging. Muon radiography is based on similar principles as X-ray radiography, measuring the surviving rate of muons escaping the target and relating it to the mass distribution inside the object. In the course of decades, after the first application in 1955, the methodology has been applied in several different fields. Muography allows us to measure the internal density distribution of the investigated object, or to simply highlight the presence of void regions by observing any excess of muons. Most of these applications require the detector to be installed below the rock being probed. In case that possible installation sites are not easily accessible by people, common instrumentation cannot be installed. A novel borehole cylindrical detector for muon radiography has been recently developed to deal with these conditions. It has been realized with a cylindrical geometry to fit typical borehole dimensions. Its design maximizes the geometrical acceptance, minimizing the dead spaces by the use of arc-shaped scintillators. The details of the construction and preliminary results of the first usage are described in this paper. © 2022 by the authors
A new cylindrical borehole detector for radiographic imaging with muons
No full textMuon radiography is a methodology which enables measuring the mass distribution within large objects. It exploits the abundant flux of cosmic muons and uses detectors with different technologies depending on the application. As the sensitive surface and geometric acceptance are two fundamental parameters for increasing the collection of muons, the optimization of the detectors is very significant. Here we show a potentially innovative detector of size and shape suitable to be inserted inside a borehole, that optimizes the sensitive area and maximizes the angular acceptance thanks to its cylindrical geometry obtained using plastic arc-shaped scintillators. Good spatial resolution is obtained with a reasonable number of channels. The dimensions of the detector make it ideal for use in 25 cm diameter wells. Detailed simulations based on Monte Carlo methods show great cavity detection capability. The detector has been tested in the laboratory, achieving overall excellent performance
Superior immunologic and therapeutic efficacy of a xenogeneic genetic cancer vaccine targeting carcinoembryonic human antigen
No full textWe have generated a xenogeneic vaccine against human carcinoembryonic antigen (hCEACAM-5 or commonly hCEA) using as immunogen rhesus CEA (rhCEA). RhCEA cDNA was codon-usage optimized (rhCEAopt) and delivered by sequential DNA electro-gene-transfer (DNA-EGT) and adenoviral (Ad) vector. RhCEAopt was capable to break tolerance to CEA in hCEA transgenic mice and immune responses were detected against epitopes distributed over the entire length of the protein. Xenovaccination with rhCEA resulted in the activation of CD4+ T-cell responses in addition to self-reactive CD8+ T-cells, the development of high-titer antibodies against hCEA, and significant antitumor effects upon challenge with hCEA+ tumor cells. The superior activity of rhCEAopt compared with hCEAopt was confirmed in hCEA/HHD double-transgenic mice, where potent CD8+ T-cell responses against specific human HLA A*0201 hCEA epitopes were detected. Our data show that xenogeneic gene-based vaccination with rhCEA is a viable approach to break tolerance against CEA, thus suggesting further development in the clinical setting
Genetic Vaccination as a Flexible Tool to Overcome the Immunological Complexity of Invasive Fungal Infections
No full textThe COVID-19 pandemic has highlighted genetic vaccination as a powerful and cost-effective tool to counteract infectious diseases. Invasive fungal infections (IFI) remain a major challenge among immune compromised patients, particularly those undergoing allogeneic hematopoietic bone marrow transplantation (HSCT) or solid organ transplant (SOT) both presenting high morbidity and mortality rates. Candidiasis and Aspergillosis are the major fungal infections among these patients and the failure of current antifungal therapies call for new therapeutic aids. Vaccination represents a valid alternative, and proof of concept of the efficacy of this approach has been provided at clinical level. This review will analyze current understanding of antifungal immunology, with a particular focus on genetic vaccination as a suitable strategy to counteract these diseases
Dedicated scanner for laboratory investigations on cone-beam CT/SPECT imaging of the breast
No full textWe describe the design, realization and basic tests of a prototype Cone-Beam Breast Computed Tomography (CBBCT) scanner, combined with a SPECT head consisting of a compact pinhole gamma camera based on a photon counting CdTe hybrid pixel detector. The instrument features a 40 μm focal spot X-ray tube, a 50 μm pitch flat panel detector and a 1-mm-thick, 55 μm pitch CdTe pixel detector. Preliminary imaging tests of the separate CT and gamma-ray units are presented showing a resolution in CT of 3.2 mm-1 at a radial distance of 50 mm from the rotation axis and that the 5 and 8 mm hot masses (99mTc labeled with a 15:1 activity ratio with respect to the background) can be detected in planar gamma-ray imaging with a contrast-to-noise ratio of about 4
A new cylindrical detector for borehole muon radiography
No full textMuons of cosmic origin have a great capability to penetrate through matter. This property is exploited in muon radiography, also known as muography, a technique which allows to highlight the presence of discontinuities of the mass density in the subsoil such as cavities, tunnels or rock masses. A detector of cylindrical geometry, optimized for borehole studies and with a diameter of 24 cm, was developed and tested. The scintillation light is read out by 384 Silicon Photomultipliers, directly coupled to the bars. The front-end and acquisition electronics, entirely housed inside the detector, are based on the EASIROC chip and are characterized by limited energy consumption (about 30 W for the entire detector). The detector has been designed in such a way as to simplify its construction as much as possible for its eventual mass production. In this article some details concerning the construction and preliminary results of measurements conducted in the Mt Echia (Naples, Italy) underground are presented
Safety and Efficacy of a Genetic Vaccine Targeting Telomerase Plus Chemotherapy for the Therapy of Canine B-Cell Lymphoma
No full textClient-owned pet dogs represent exceptional translational models for advancement of cancer research because they reflect the complex heterogeneity observed in human cancer. We have recently shown that a genetic vaccine targeting dog telomerase reverse transcriptase (dTERT) and based on adenovirus DNA electro-gene-transfer (Ad/DNA-EGT) technology can induce strong cell-mediated immune responses against this tumor antigen and increase overall survival of dogs affected by B-cell lymphosarcoma (LSA) in comparison with historical controls when combined with a cyclophosphamide, vincristine, and prednisone (COP) chemotherapy regimen. Here, we have conducted a double-arm clinical trial with an extended number of LSA patients, measured the antigen specific immune response, and evaluated potential toxic effects of the immunotherapy along with a follow-up of patients survival for 3.5 years. The immune response was measured by enzyme-linked immunospot assay. The expression of dTERT was quantified by quantitative polymerase chain reaction. Changes in hematological parameters, local/systemic toxicity or organic dysfunction and fever were monitored over time during the
treatment. dTERT-specific cell-mediated immune responses were induced in almost all treated animals. No adverse effects were observed in any dog patient that underwent treatment. The overall survival time of vaccine/COP-treated dogs was significantly increased over the COP-only cohort (> 76.1 vs. 29.3 weeks, respectively, p < 0.0001). There was a significant association between dTERT expression levels in LSA cells and overall survival among vaccinated patients. In conclusion, Ad/DNA-EGT-based cancer vaccine against dTERT
in combination with COP chemotherapy is safe and significantly prolongs the survival of LSA canine patients.
These data confirm the therapeutic efficacy of dTERT vaccine and support the evaluation of this approach for other cancer types as well as the translation of this approach to human clinical trials
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