Single Cell Technologies to Dissect Heterogenous Immune Cell Therapy Products.

Single cell tools have dramatically transformed the life sciences; concurrently, autologous and allogeneic immune cell therapies have recently entered the clinic. Here we discuss methods, applications, and considerations for single cell technologies in the context of immune cell manufacturing. Molecular heterogeneity can be profiled at the level of the genome, epigenome, transcriptome, proteome, metabolome, and antigen receptor repertoire, in isolation or in tandem through multi-omic approaches. Such data inform heterogeneity within cell products and can be linked to potency readouts and clinical data, with the ultimate goal of identifying Critical Quality Attributes to predict patient outcomes. Non-destructive approaches hold promise for monitoring cell state and analyzing the impacts of gene edits within engineered products. Destructive omics approaches could be combined with non-destructive technologies to predict therapeutic potency. These technologies are poised to redefine cell manufacturing toward rapid, cost-effective, and high-throughput methods to detect and respond to dynamic cell states.