Naive T cell deficits at diagnosis and after chemotherapy impair cell therapy potential in pediatric cancers [Research Briefs]

Translational data on chimeric antigen receptor (CAR) T cell trials indicates the presence of naive T cells in the pre-manufacture product is important to clinical response and persistence. In anticipation of developing CAR trials for other tumors, we investigated the T cell distribution from children with solid tumors and lymphomas at diagnosis and after every cycle of chemotherapy. We found that patients with T cells enriched for naive and stem central memory cells expanded well in vitro, but the majority of tumor types showed chemotherapy related depletion of early lineage cells with a corresponding decline in successful ex vivo stimulation response. Unexpectedly, many pediatric solid tumor patients had low numbers of Naive T cells prior to any therapy. These data indicate the ex vivo manufacture of CAR T cells may need to be customized based on the nature of T cells available in each disease type.

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