A significant fraction of CART batches fail every year due to slow Tcell growth rates during the expansion step of the process. Furthermore, the starting material for every batch differs in many ways including the distribution of phenotypes in the Tcell population, yet the final product specification is fixed. Tcell growth rates can be effected by levels of cytokines and different Tcell phenotypes respond differently to these growth factors. In this study, the growth rates of important CD4+ and CD8+ Tcell phenotypes (i.e. Tnaive, Teff, Tcm) were evaluated and modelled as a function of cytokine (Il2, Il7 and Il15) level. Cell health was assessed via an Annexin V-propidium iodide assay, and phenotype was determined via Flow Cytometry. The results indicate significant variation between the different Tcell phenotypes in terms of how their growth and health is affected by different levels of the different cytokines. Interestingly, all of the Tcell phenotypes in varying degrees exhibited a reduction in cell numbers in the first day or two following vial thaw and bead-induced activation. Immediately following that period, effector memory cells in general grew faster than the other phenotypes. Interestingly optimal growth rates were observed at intermediate cytokine levels, a result that is helpful in keeping process costs down. A fuzzy model employed effectively predicted how the Tcell growth rates varied with the different combinations of cytokines, and transcriptomics data helped to inform the model on metabolic activities relating to cell growth. Some of the experiments involved mixed culture of different Tcell phenotypes, to assess how interaction between Tcells effects their growth.

Effect of key cytokines on the growth of different T cell phenotypes

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.