An integrated perspective on measuring cytokines to inform CAR-T bioprocessing.

Chimeric antigen receptor (CAR)-T cells are emerging as a generation-defining therapeutic however their manufacture remains a major barrier to meeting increased market demand. Monitoring critical quality attributes (CQAs) and critical process parameters (CPPs) during manufacture would vastly enrich acquired information related to the process and product, providing feedback to enable real-time decision making. Here we identify specific CAR-T cytokines as value-adding analytes and discuss their roles as plausible CPPs and CQAs. High sensitivity sensing technologies which can be easily integrated into manufacture workflows are essential to implement real-time monitoring of these cytokines. We therefore present biosensors as enabling technologies and evaluate recent advancements in cytokine detection in cell cultures, offering promising translatability to CAR-T biomanufacture. Finally, we outline emerging sensing technologies with future promise, and provide an overall outlook on existing gaps to implementation and the optimal sensing platform to enable cytokine monitoring in CAR-T biomanufacture.

Discovery of selective monosaccharide receptors via dynamic combinatorial chemistry.

The molecular recognition of saccharides by synthetic hosts has become an appealing but elusive task in the last decades. Herein, we combine Dynamic Combinatorial Chemistry (DCC) for the rapid self-assembly and screening of virtual libraries of receptors, with the use of ITC and NMR to validate the hits and molecular modelling to understand the binding mechanisms. We discovered a minimalistic receptor, 1F (N-benzyl-L-phenylalanine), with considerable affinity for fructose (Ka = 1762 M-1) and remarkable selectivity (>50-fold) over other common monosaccharides. The approach accelerates the discovery process of receptors for saccharides.