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Cancer Discov. 2019 Jan 10. pii: CD-18-1314. doi: 10.1158/2159-8290.CD-18-1314. [Epub ahead of print]

Naive T cell deficits at diagnosis and after chemotherapy impair cell therapy potential in pediatric cancers.

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Children's Hospital of Philadelphia.
Immunotherapy, Children's Hospital of Philadelphia.
Division of Oncology, Children's Hospital of Philadelphia.
Division of Oncology, Children's Hospital of Philadelphia


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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