1. Expression of inducible factors reprograms CAR-T cells for enhanced function and safetyAnže Smole, Alexander Benton, Mathilde A. Poussin, Monika A. Eiva, Claudia Mezzanotte, 2022, original scientific article Abstract: Despite the success of CAR-T cell cancer immunotherapy, challenges in efficacy and safety remain. Investigators have begun to enhance CAR-T cells with the expression of accessory molecules to address these challenges. Current systems rely on constitutive transgene expression or multiple viral vectors, resulting in unregulated response and product heterogeneity. Here, we develop a genetic platform that combines autonomous antigen-induced production of an accessory molecule with constitutive CAR expression in a single lentiviral vector called Uni-Vect. The broad therapeutic application of Uni-Vect is demonstrated in vivo by activation-dependent expression of (1) an immunostimulatory cytokine that improves efficacy, (2) an antibody that ameliorates cytokine-release syndrome, and (3) transcription factors that modulate T cell biology. Uni-Vect is also implemented as a platform to characterize immune receptors. Overall, we demonstrate that Uni-Vect provides a foundation for a more clinically actionable next-generation cellular immunotherapy.
Keywords: CAR-T cells, TCR, inducible, transcription factor, NFAT, single lentiviral expression system, IL-6, IL-12, CRS, armored
Published in DiRROS: 18.07.2024; Views: 142; Downloads: 25
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4. Fire safety assessment of sprinkler systems for car parks using the J-value methodologyMalika Alimzhanova, Michael Spearpoint, Grunde Jomaas, 2022, original scientific article Abstract: A J-value assessment was carried out to quantify the costs and benefits of sprinkler system installation in car parks, both with respect to life safety and property protection. Nine scenarios were established based on collected input data. All car park types were considered for the USA, England, Scotland, Wales and the UK nations collectively, while separate considerations were made for multi-storey car parks (MSCPs) in the UK and for MSCPs, underground and other parking types in England.
Even when assuming 100% sprinkler effectiveness, the J-values for the nine scenarios were all larger than unity (ranging from 5 to 555), thus indicating that the installation of sprinklers is not a cost-effective investment for car parks from a societal point of view. The analysis showed that different car park types must be treated separately, due to specifics of structure and fire statistics. The lowest J-values were obtained for MSCPs and underground car parks. Sprinkler installation mainly provides property protection benefits, because of property loss savings substantially outweigh those associated with life safety.
Even though sprinklers were not cost-effective for car parks in the current analysis, the scarcity of data and new emerging technologies suggests that further investigation is needed.
Keywords: cost-benefit analysis, J-value, life quality index, Car parks, Sprinkler systems
Published in DiRROS: 09.01.2024; Views: 363; Downloads: 136
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