Resistance to chimaeric antigen receptor (CAR) T cell therapy develops through multiple mechanisms, most notably antigen loss and tumour-induced immune suppression. It has been suggested that T cells expressing multiple CARs may overcome the resistance of tumours and that T cells expressing receptors that switch inhibitory immune-checkpoint signals into costimulatory signals may enhance the activity of the T cells in the tumour microenvironment. However, engineering multiple features into a single T cell product is difficult because of the transgene-packaging constraints of current gene-delivery vectors.
View Article and Find Full Text PDFAs machines powered by artificial intelligence increase in their technological capacities, there is a growing interest in the theoretical and practical idea of artificial moral advisors (AMAs): systems powered by artificial intelligence that are explicitly designed to assist humans in making ethical decisions. Across four pre-registered studies (total N = 2604) we investigated how people perceive and trust artificial moral advisors compared to human advisors. Extending previous work on algorithmic aversion, we show that people have a significant aversion to AMAs (vs humans) giving moral advice, while also showing that this is particularly the case when advisors - human and AI alike - gave advice based on utilitarian principles.
View Article and Find Full Text PDFFlavin-containing monooxygenases (FMOs) are present in most organisms including plants, fungi, bacteria, invertebrates and vertebrates, where they catalyse the oxidative metabolism of a range of xenobiotics and endogenous metabolites. FMOs have been associated with ageing and longevity in the mouse and in C. elegans.
View Article and Find Full Text PDFMol Ther Methods Clin Dev
December 2024
Adeno-associated virus (AAV) is a widely used vehicle for gene delivery, lending interest to developing methods for enhancing AAV transduction and transgene expression. Here, we profile the function of several topoisomerase poisons, which are small molecules that stabilize topoisomerase enzymatic intermediates, where topoisomerase enzymes are covalently bound at chromosomal DNA breaks. As previously observed, we found that the topoisomerase poisons camptothecin (CPT), doxorubicin (DOX), and etoposide (ETO) increased AAV transduction in cultured cell models.
View Article and Find Full Text PDFAdv Biochem Eng Biotechnol
November 2024