Dosimetria in campo misto presso la facility CLEAR del CERN

Questo lavoro presenta la campagna di misure del campo di radiazioni secondario in prossimità della facility CLEAR del CERN. Il fascio principale è composto da treni di elettroni a 200 MeV, fermati da un bersaglio in piombo e cemento. Le misure sono state effettuate in cinque posizioni per tre valori di carica accelerata per treno di impulsi, utilizzando rivelatori a termoluminescenza (TLD) e luminescenza otticamente stimolata (OSL) per il campo fotonico, e rivelatori a tracce (CR39) per il campo neutronico. La caratterizzazione del campo fotonico ha evidenziato un buon accordo tra TLD e OSL, con differenze tra le letture imputabili alla dose da elettroni dovuta alle perdite di fascio e alla radiazione diffusa. Entrambi gli strumenti, tuttavia hanno evidenziato una sovrastima della dose rispetto all’andamento lineare atteso per alte intensità del fascio primario. I CR39 impiegati per la caratterizzazione del campo neutronico hanno evidenziato una risposta pressoché lineare, con una sovrastima dell’andamento lineare solo in una posizione, e comunque molto meno evidente rispetto al caso dei dosimetri fotonici. Per spiegare l’origine di questo comportamento inatteso si ipotizza la presenza di una corrente di buio di energia inferiore al fascio, tale da generare un segnale fotonico non accompagnato da una significativa produzione di fotoneutroni

Volontariamente. Esperienze di crescita e solidarietà nel servizio civile in Piemonte

Una ricerca promossa dalla Regione Piemonte e realizzata per Federsolidarietà. Il Servizio Civile volontario rappresenta un’opportunità, per i giovani che la scelgono, di vivere un’esperienza in grado di arricchirli e di avvicinarli al mondo della solidarietà sociale; per gli enti, di ideare progetti di servizio alla collettività altrimenti non realizzabili.- Indice #4- Premessa, Marco Demarie #6- Presentazione, Elide Tisi #8- Il servizio civile in Piemonte è una realtà, Teresa Angela Migliasso #10- 1. Una storia di valori e partecipazione, Gianfranco Marocchi #12- 2. La ricerca #22- 3. Appendice #11

P09.01 Adoptive cell therapy of hematological malignancies using cytokine-induced killer cells retargeted with monoclonal antibodies

Background Cytokine-Induced Killer (CIK) cells are a population of effector cells that represents a promising tool for adoptive cell therapy. They are easily expandable ex-vivo, safe, and exert cytotoxicity against a broad range of tumor histotypes.1 We recently reported that they have a relevant expression of FcγRIIIa (CD16a), which can be exploited in combination with clinical-grade monoclonal antibodies (mAbs) to redirect their cytotoxicity in an antigen-specific manner, to improve their antitumor activity.2 Indeed, the engagement of CD16a on CIK cells leads to a potent antibody-dependent cell-mediated cytotoxicity (ADCC) against ovarian cancer both in vitro and in vivo. Based on this observation, we investigated whether CIK cells can be specifically retargeted against B-cell malignancies by combination with anti-CD20 mAbs, namely Rituximab® (RTX) and Obinutuzumab® (OBI). Materials and Methods CIK cells were obtained from peripheral blood mononuclear cells of healthy donors, and stimulated in vitro with IFN-γ, CD3 mAb and IL-2 for 14 days; fresh IL-2 was provided every 3–4 days. CIK cell phenotype was analyzed by multicolor flow cytometry; cytotoxic activity was assessed by calcein AM-release assay against B-cell lines, primary samples and patient-derived xenografts (PDX) obtained from B-cell lymphoma patients after written informed consent. Results The combination with both RTX and OBI significantly increased specific CIK cells lysis against several CD20-expressing lymphoma B cell lines, primary tumors from B-cell lymphoma patients and an established PDX, compared to the combination with a control mAb (cetuximab, CTX). NK-depletion demonstrated that the mAb-mediated cytotoxicity is accountable to the CIK cells fraction within the bulk population since no difference in the lytic activity was detectd in the absence of NK cells. In addition, these results are further supported by in vivo preliminary experiments where the treatment with CIK cells in combination with OBI extensively reduced the growth of PDX and increased mice survival, compared to CIK cells or OBI administered alone. Conclusions Here we proved that CIK cells can be retargeted with clinical-grade mAbs against CD20-expressing lymphomas. These data indicate that the combination of CIK cells with mAbs can represent a novel approach for the treatment of haematological malignancies. References Franceschetti M, Pievani A, Borleri G, Vago L, Fleischhauer K, Golay J, et al. Cytokine-induced killer cells are terminally differentiated activated CD8 cytotoxic T-EMRA lymphocytes. Exp Hematol 2009;37:616–28. Cappuzzello E, Tosi A, Zanovello P, Sommaggio R, Rosato A. Retargeting cytokine-induced killer cell activity by CD16 engagement with clinical-grade antibodies. Oncoimmunology 2016 Aug;5(8):e1199311. The research leading to these results has received funding from Fondazione AIRC under IG 2018 - ID. 21354 project - P.I. Rosato Antonio Disclosure Information A. Dalla Pieta: None. E. Cappuzzello: None. P. Palmerini: None. R. Sommaggio: None. G. Astori: None. K. Chieregato: None. O. Perbellini: None. M. Tisi: None. C. Visco: None. M. Ruggeri: None. A. Rosato: None

P09.13 Optimization of a GMP-grade large-scale expansion protocol for cytokine-induced killer cells using gas-permeable static culture flasks

Background Cytokine-Induced Killer (CIK) cells are ex vivo expanded T cells with NK cell phenotype. They express both CD3 and CD56 antigens, and exert a potent antitumor activity against a variety of tumors. Several clinical trials demonstrated the safety and the feasibility of CIK cell therapy, with very low side effects and minimal graft-versus-host toxicity. In this study, we developed a GMP-compliant protocol for robust large-scale expansion of CIK cells using G-Rex® gas-permeable static culture flasks. Materials and Methods CIK cells were obtained by stimulating healthy donor PBMCs with GMP-grade IFN-γ, IL-2 and CD3 mAbs, and were cultured in G-Rex6® or G-Rex®6M well plates. CIK cells in G-Rex6® were split only once at day 7 to reduce cell density, whereas the number of CIK cells culterd in G-Rex®6M was not adjusted. In both culture conditions, fresh IL-2 was provided every 3–4 days. We compared these two culture protocols with the culture in standard flasks. Phenotype was analyzed by flow cytometry and cytotoxicity was assessed against several tumor cell lines by calcein-release assay. Results CIK cells cultured in G-Rex6® well plates showed an outstanding cell expansion compared to G-Rex®6M well plates or standard culture flasks, with a 400-fold expansion and a mean of 109 total cells obtained per single well in 14 days, starting from just 2.5 × 106 cells per well. Moreover, the cultures in G-Rex6® were characterized by an higher percentage of CD3+CD56+ cells, as compared to G-Rex®6M or standard culture flasks. Cells cultured in all devices had a comparable expression of NKG2D, NKp30, NKp44, 2B4 receptors. Importantly, CIK cells expanded in G-Rex®6 were as cytotoxic as cells expanded in standard culture flasks. Conversely, CIK cells cultured in G-Rex®6M showed a remarkable reduction of cytotoxicity against tumor cell targets, thus suggesting that cell density during expansion could affect CIK cell activity. Conclusions We propose a GMP-compliant protocol for robust large-scale production of CIK cells. G-Rex® system allows to obtain large amounts of CIK cells highly enriched in the CD3+CD56+ subset and endowed with high cytotoxic activity; this can be accomplished with just a single cell culture split at day 7, which dramatically reduces the culture manipulation as compared to the standard culture flasks. Notably, this strategy can be further and easily scalable to produce CIK cells for clinical immunotherapy applications. Disclosure Information A. Ventura: None. P. Palmerini: None. A. Dalla Pieta: None. R. Sommaggio: None. G. Astori: None. K. Chieregato: None. M. Tisi: None. C. Visco: None. O. Perbellini: None. M. Ruggeri: None. E. Cappuzzello: None. A. Rosato: None

Clinical characteristics and risk factors associated with COVID-19 severity in patients with haematological malignancies in Italy: a retrospective, multicentre, cohort study

Several small studies on patients with COVID-19 and haematological malignancies are available showing a high mortality in this population. The Italian Hematology Alliance on COVID-19 aimed to collect data from adult patients with haematological malignancies who required hospitalisation for COVID-19

Search computing: A model-driven perspective

none3Volume 6142/2010Marco Brambilla; Stefano Ceri; Massimo TisiBrambilla, Marco; Ceri, Stefano; Tisi, Massim

A Metamodel Transformation Framework for the Migration of WebML models to MDA

Abstract. Traditional methodologies in Model Driven Web Engineering, like WebML, are based on domain specific modeling languages. A Web application is usually designed using several Domain Specific Models (DSM), often based on different formalisms and abstraction levels. In this paper we propose a model-driven procedure for integrating pre-MDA DSMs within the MDA framework. The DSMs, originally expressed in different formalisms, are translated into a unified representation that conforms to a MDA metamodel. The procedure, given the definition of suitable model transformations, is completely automatic. The proposed framework is fully implemented for the WebML metamodel and can be generalized to other Web engineering approaches.

Search Computing: A Model-Driven Perspective

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