Process development and manufacture of primary human T-cells in scalable, automated stirred-tank bioreactors

Engineered Chimeric Antigen Receptor (CAR) T-cell products have recently gained FDA and EMA approval and have demonstrated significant clinical efficacy against non-Hodgkin lymphoma and pediatric B-cell acute lymphoblastic leukemia. Despite the significant clinical and commercial progress these products represent, the high costs associated with patient-specific cell therapy manufacture needs to be addressed. The work presented here focuses on the growth of human primary T-cells and CAR-T cells across a range of commercially available expansion platforms, including stirred tank bioreactors, which although routinely employed for the production of biologics, are not commonly used for the manufacture of T-cells. Initial experimental studies were carried out in an automated ambr® 250 single use bioreactor system which has demonstrated significant success for suspension and adherent mammalian cell culture applications. Building on previous work undertaken in the group which developed a new bioreactor vessel for microcarrier culture, both the new and existing bioreactor vessels were characterized with respect to cell yield, fold expansion, viability, metabolite profile, T-cell subpopulations and kLa. The comparison between the two vessels was performed based on power per unit volume, kLa and stirring speed, ranging from 100 to 200 rpm, using at least 3 different donors per condition. Please click Additional Files below to see the full abstract

Autoimmune thyroid diseases in patients treated with alemtuzumab for multiple sclerosis: An example of selective anti-TSH-receptor immune response

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for the treatment of active relapsing-remitting multiple sclerosis (MS). Alemtuzumab induces a rapid and prolonged depletion of lymphocytes from the circulation, which results in a profound immuno-suppression status followed by an immune reconstitution phase. Secondary to reconstitution autoimmune diseases represent the most common side effect of Alemtuzumab treatment. Among them, Graves' disease (GD) is the most frequent one with an estimated prevalence ranging from 16.7 to 41.0% of MS patients receiving Alemtuzumab. Thyrotropin (TSH) receptor (R)-reactive B cells are typically observed in GD and eventually present this autoantigen to T-cells, which, in turn, secrete several pro-inflammatory cytokines and chemokines. Given that reconstitution autoimmunity is more frequently characterized by autoantibody-mediated diseases rather than by destructive Th1-mediated disorders, it is not surprising that GD is the most commonly reported side effect of Alemtuzumab treatment in patients with MS. On the other hand, immune reconstitution GD was not observed in a large series of patients with rheumatoid arthritis treated with Alemtuzumab. This negative finding supports the view that patients with MS are intrinsically more at risk for developing Alemtuzumab-related thyroid dysfunctions and in particular of GD. From a clinical point of view, Alemtuzumab-induced GD is characterized by a surprisingly high rate of remission, both spontaneous and after antithyroid drugs, as well as by a spontaneous shift to hypothyroidism, which is supposed to result from a change from stimulating to blocking TSH-receptor antibodies. These immune and clinical peculiarities support the concept that antithyroid drugs should be the first-line treatment in Alemtuzumab-induced Graves' hyperthyroidism

Development and testing of advanced methods for the screening of Enhanced-Oil-Recovery techniques

Enhanced Oil Recovery (EOR) techniques must undergo preliminary laboratory and pilot testing before implementation to field-wide scale, and the whole evaluation process requires heavy investments. Hence forecasting EOR potential is a key decision-making element. A critical difference amongst EOR techniques resides in the oil-displacement mechanism upon which they are based. The effectiveness of these mechanisms depends on oil and reservoir properties. As such, similar EOR techniques are typically successful in fields sharing similar features. Here we implement and test a screening method aimed at estimating the optimal EOR technique for a target reservoir. Our approach relies on the information content tied to an exhaustive set of EOR field experiences. The basic screening criterion is the analogy with known reservoir settings in terms of oil and formation properties. Analogy is assessed by grouping fields into clusters: we rely on a Bayesian hierarchical clustering algorithm, whose main advantage is that the number of clusters is not set a priori but stems from data statistics. As a test bed, we perform a blind test of our screening approach by considering 2 fields operated by eni. Our predictions for analogy assessment are in agreement with the EOR techniques applied or planned in these fields

Ireland

This report is part of the project The Factbook on the Illicit Trade in Tobacco Products.It focuses on Ireland, where the illicit trade in tobacco products has been an important concern since 2007\u20132008. According to unofficial estimates, 29.7% of total tobacco consumption was illicit in 2012, when Ireland ranked 3rd (after Latvia and Lithuania) among 22 European countries for illicit tobacco penetration (Euromonitor International 2013a). To tackle the ITTP, the Revenue Commissioners have launched the Revenue\u2019s Strategy on Combating the Illicit Tobacco Trade (2011\u20132013), the aim of which is to deter people from buying illicit trade products and to reduce their availability. Given the close geographical (shared land border), social, economic and cultural connections, the report also focuses, where appropriate, on Northern Ireland, a part of the United Kingdom

Spain

This report is part of the project The Factbook on the Illicit Trade in Tobacco Products (hereafter ITTP). It focuses on Spain, where the illicit trade in tobacco products is an emerging issue, particularly in certain regions. After tax increases in 2009-2010, Spain became a destination market of illicit tobacco and the ITTP penetration peaked at 8.8% in 2013. Nevertheless, the ITTP level is lower than the European average. In the past, ITTP penetration had decreased from 6% to almost 1% between 1998 and 2010, due to the successful enforcement actions against contraband. Spain used to be a transit country

Italy

This report is part of the project The Factbook on the Illicit Trade in Tobacco Products. It focuses on Italy, where the illicit trade in tobacco seems to have grown in recent years. This fact, combined with the geographical location of the country and the consolidated presence of organised crime, makes Italy an interesting country to explore in terms of ITTP flows in the Mediterranean basin and towards North European countries

France

This report provides the French country profile of the project The Factbook on the Illicit Trade in Tobacco Products. In France, the illicit trade in tobacco products is a key issue due to its high penetration in the French tobacco market, reaching 14.7% of total consumption in 2014 (KPMG 2015). Tobacco control policies are at the top of the French policy agenda, and a national action plans against the ITTP was launched in 2011. Moreover, the recent ratification of the Protocol Against Illicit Trade in Tobacco Products (WHO FCTC), in November 2015, demonstrates France’s commitment to tackling the illicit trade. The growing attention of the French Customs to tobacco smuggling is evidenced by the increasing number of seizures

Lithuania

This report is part of the project The Factbook on the Illicit Trade in Tobacco Products(henceforth ITTP)

Prevedere i furti in abitazione

Il contributo presenta i risultati di una sperimentazione condotta nelle città di Milano, Roma e Bari sull'utilizzo di mappe previsionali della criminalità attraverso la tecnica del Risk Terrain ModelingThe report presents the results about the use of predictive mapping on burglary in three Italian cities (Milan, Rome and Bari)

Introduzione alle misure con smartphone: esperienza di misura dell'accelerazione gravitazionale g con l'uso di un pendolo semplice

Viene descritta l’attività svolta, di supporto al progetto "LAB2GO”: aiuto alla diffusione della pratica laboratoriale nella scuola" che ha permesso di realizzare un’esperienza di Fisica per la misura dell'accelerazione gravitazionale "g" con l’uso di uno smartphone. Nella relazione vengono spiegate le tecniche sperimentali utilizzate ed indicati i risultati ottenuti effettuando misure di oscillazioni di pendoli, semplici realizzati per l'occasione, sfruttando diverse app sviluppate per smartphone. Viene infine indicata un'analisi critica dei risultati ottenuti con suggerimenti per chiunque volesse ripetere e migliorare l'esperienza