A standardized T cell backbone panel for immune monitoring of adoptively transferred cellular therapies

CYTO 2024 -- Adoptive cell therapies (ACT) have emerged as a promising frontier in cancer and autoimmune disorders, harnessing the power of the immune system to combat diseases. However, the full potential of ACT remains elusive, often hindered by challenges such as variable patient responses and limited persistence of infused cells. It is imperative to understand the deep cellular immune phenotypes of these therapies pre- and post-infusion to elucidate what aspects of the infused cells correlate with persistence and positive clinical outcome. In this context, we explored how deep phenotyping facilitates the identification of key cellular biomarkers influencing ACT efficacy by validating and launching a 22-marker flow cytometry panel. The panel includes biomarkers that allow the monitoring of naive, memory, effector T cell subsets, regulatory T cells, activation/exhaustion biomarkers and quiescent cells, which are known to have proliferative capacity. Frequency and event counts are currently reported, but with the addition of a dual-platform CD45 Trucount? and quantitation standards, both absolute cells per microliter and/or equivalent reference fluorophores (ERF) for checkpoint markers can be determined. This panel was built so the ACT-specific detection reagents can be switched with detection reagents directed against new products without disrupting performance of the backbone panel with regards to maintaining specificity, sensitivity and spillover characteristics. In addition, the panel allows for the phenotyping of the native cells in conjunction with that of the adoptively transferred cell therapy pre- and post-infusion.