Abstract
Chimeric antigen receptor T cell therapy, also known as CAR T cell therapy, has been shown to have significant clinical efficacy for B-cell malignancies by genetically engineering autologous cells to attack cancer cells when infused into patients [1]. However recently, using an ingeniously developed CRISPR-Cas9 loss of function technique performed on acute lymphoblastic cells, investigators have interrogated clinical samples and revealed a correlation between death receptor gene expression, including FADD and BID, in pre-treatment samples and response after CART19 [2]. They have identified that impairments in leukemia and lymphoma death receptor signaling lead to primary CART19 resistance, which in turn mediate progressive CAR T cell functional impairment, revealing a novel mechanism of resistance against CAR T cell therapy. The authors also performed transcriptomic and epigenomic profiles on these cells and uncovered clustered gene expression profiles and areas of chromatin accessibility using ATAC-Seq between responsive and unresponsive cells [2].
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