Preclinical development of HIvax: human survivin Highly Immunogenic vaccines

Our previous work involved the development of a recombinant fowlpox virus encoding survivin (FP-surv) vaccine that was evaluated for efficacy in mesothelioma mouse models. Results showed that FP-surv vaccination generated significant immune responses, which led to delayed tumor growth and improved animal survival. We have extended those previous findings in the current study, which involves the pre-clinical development of an optimized version of FP-surv designed for human immunization (HIvax). Survivin-derived peptides for the most common haplotypes in the human population were identified and their immunogenicity confirmed in co-culture experiments using dendritic cells and T cells isolated from healthy donors. Peptides confirmed to induce CD8(+) and CD4(+) T cells activation in humans were then included in 2 transgenes optimized for presentation of processed peptides on MHC-I (HIvax1) and MHC-II (HIvax2). Fowlpox vectors expressing the HIvax transgenes were then generated and their efficacy was evaluated with subsequent co-culture experiments to measure interferon-γ and granzyme B secretion. In these experiments, both antigen specific CD4(+) and CD8(+) T cells were activated by HIvax vaccines with resultant cytotoxic activity against survivin-overexpressing mesothelioma cancer cells. These results provide a rationale for clinical testing of HIvax1 and HIvax2 vaccines in patients with survivin-expressing cancers

Multi-antigen Vaccination With Simultaneous Engagement of the OX40 Receptor Delays Malignant Mesothelioma Growth and Increases Survival in Animal Models

Malignant Mesothelioma (MM) is a rare and highly aggressive cancer that develops from mesothelial cells lining the pleura and other internal cavities, and is often associated with asbestos exposure. To date, no effective treatments have been made available for this pathology. Herein, we propose a novel immunotherapeutic approach based on a unique vaccine targeting a series of antigens that we found expressed in different MM tumors, but largely undetectable in normal tissues. This vaccine, that we term p-Tvax, is comprised of a series of immunogenic peptides presented by both MHC-I and -II to generate robust immune responses. The peptides were designed using in silico algorithms that discriminate between highly immunogenic T cell epitopes and other harmful epitopes, such as suppressive regulatory T cell epitopes and autoimmune epitopes. Vaccination of mice with p-Tvax led to antigen-specific immune responses that involved both CD8+ and CD4+ T cells, which exhibited cytolytic activity against MM cells in vitro. In mice carrying MM tumors, p-Tvax increased tumor infiltration of CD4+ T cells. Moreover, combining p-Tvax with an OX40 agonist led to decreased tumor growth and increased survival. Mice treated with this combination immunotherapy displayed higher numbers of tumor-infiltrating CD8+ and CD4+ T cells and reduced T regulatory cells in tumors. Collectively, these data suggest that the combination of p-Tvax with an OX40 agonist could be an effective strategy for MM treatment

Goodbye Hartmann trial: a prospective, international, multicenter, observational study on the current use of a surgical procedure developed a century ago

Background: Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann's procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods: This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results: 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P < 0.001). 30-day mortality was higher in HP patients (13.7%), especially in case of bowel perforation and diffused peritonitis. 1-year follow-up showed no differences on ostomy reversal rate between HP and RPA. (P = 0.127). A backward likelihood logistic regression model showed that RPA was preferred in younger patients, having low ASA score (≤ 3), in case of large bowel obstruction, absence of colonic ischemia, longer time from admission to surgery, operating early at the day working hours, by a surgeon who performed more than 50 colorectal resections. Conclusions: After 100 years since the first Hartmann's procedure, HP remains the most common treatment for left-sided colorectal emergencies. Treatment's choice depends on patient characteristics, the time of surgery and the experience of the surgeon. RPA should be considered as the gold standard for surgery, with HP being an exception

Il Futuro della Cybersecurity in Italia: Ambiti Progettuali Strategici

Il presente volume nasce come continuazione del precedente, con l’obiettivo di delineare un insieme di ambiti progettuali e di azioni che la comunità nazionale della ricerca ritiene essenziali a complemento e a supporto di quelli previsti nel DPCM Gentiloni in materia di sicurezza cibernetica, pubblicato nel febbraio del 2017. La lettura non richiede particolari conoscenze tecniche; il testo è fruibile da chiunque utilizzi strumenti informatici o navighi in rete. Nel volume vengono considerati molteplici aspetti della cybersecurity, che vanno dalla definizione di infrastrutture e centri necessari a organizzare la difesa alle azioni e alle tecnologie da sviluppare per essere protetti al meglio, dall’individuazione delle principali tecnologie da difendere alla proposta di un insieme di azioni orizzontali per la formazione, la sensibilizzazione e la gestione dei rischi. Gli ambiti progettuali e le azioni, che noi speriamo possano svilupparsi nei prossimi anni in Italia, sono poi accompagnate da una serie di raccomandazioni agli organi preposti per affrontare al meglio, e da Paese consapevole, la sfida della trasformazione digitale. Le raccomandazioni non intendono essere esaustive, ma vanno a toccare dei punti che riteniamo essenziali per una corretta implementazione di una politica di sicurezza cibernetica a livello nazionale. Politica che, per sua natura, dovrà necessariamente essere dinamica e in continua evoluzione in base ai cambiamenti tecnologici, normativi, sociali e geopolitici. All’interno del volume, sono riportati dei riquadri con sfondo violetto o grigio; i primi sono usati nel capitolo introduttivo e nelle conclusioni per mettere in evidenza alcuni concetti ritenuti importanti, i secondi sono usati negli altri capitoli per spiegare il significato di alcuni termini tecnici comunemente utilizzati dagli addetti ai lavori. In conclusione, ringraziamo tutti i colleghi che hanno contribuito a questo volume: un gruppo di oltre 120 ricercatori, provenienti da circa 40 tra Enti di Ricerca e Università, unico per numerosità ed eccellenza, che rappresenta il meglio della ricerca in Italia nel settore della cybersecurity. Un grazie speciale va a Gabriella Caramagno e ad Angela Miola che hanno contribuito a tutte le fasi di produzione del libro. Tra i ringraziamenti ci fa piacere aggiungere il supporto ottenuto dai partecipanti al progetto FILIERASICURA

Towards supporting fine-grained access control for Grid Resources

The heterogeneous nature and independent administration of geographically dispersed resources in Grid, demand the need for access control using fine-grained policies. In this paper, we investigate the problem of fine-grained access control in the context of resource allocation in Grid, as we believe it is the first and key step in developing access control methods specifically tailored for Grid systems. To perform this access control, we design a security component (to be part of a meta-scheduler service) that finds the list of nodes where a user is authorized to run his/her jobs. The security component is designed in an effort to reduce the number of rules that need to be evaluated for each user request

A semantic approach to build personalized interfaces in the cultural heritage domain

In this paper we present a system we have built to disseminate cultural heritage distributed across multiple museums. Our system addresses the requirements of two categories of users: the end users that need to access information according to their interests and interaction preferences, and the domain experts and museum curators that need to develop thematic tours providing end users with a better understanding of the single artefact or collection. In our approach we make use of a semantic representation of the given heritage domain in order to build multiple visual interfaces, called Virtual Wings (VWs). Such interfaces allow users to navigate through data available from digital archives and thematic tours and to create their own personalized virtual visits. An interactive application integrating personalized digital guides (using PDAs) and 360 panoramic images is the example of VW presented

XACML Policy Integration Algorithms

XACML is the OASIS standard language specifically aimed at the specification of authorization policies. While XACML fits well with the security requirements of a single enterprise (even if large and composed by multiple departments), it does not address the requirements of virtual enterprises in which several autonomous subjects collaborate by sharing their resources to provide better services to customers. In this article we highlight such limitation, and we propose an XACML extension, the policy integration algorithms, to address them. In the article we also present the implementation of a system that makes use of the policy integration algorithms to securely replicate information in a P2P-like environment. In our solution, the data replication process considers the policies specified by both the owners of the data shared and the peers sharing data storage