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One of the most exciting immune therapies is the use of a patient’s T cells modified in the lab with a chimeric antigen receptor (CAR) to retarget T cells to cancer cells. CAR T cells targeting CD19 were a breakthrough therapy in treatment of children with leukemia, leading to the first FDA approval of a gene modified cell therapy. But learning why the children had such success is key to expanding CAR T therapy.
To answer this question, we investigated the immune system of pediatric patients with cancer. Specifically, we focused on the quality of the cells collected from patients and how they differed among children with long- or short-lasting responses. Children naturally possess a high amount of Naïve T cells, which are also functionally very young compared to those of adults. This high level of Naïve T cells correlated with better downstream CAR function and response-- but not always. Deeper biologic investigation spurred by this finding reveals subtle immune dysfunction in T cells of children with cancer that are exacerbated by intense chemotherapy.
These findings are informing a better understanding of immune function in cancer and how to address cancer-specific dysfunction that may hold back effective immunotherapy.
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