Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy.
Integrative Bulk and Single-Cell Profiling of Premanufacture T-cell Populations Reveals Factors Mediating Long-Term Persistence of CAR T-cell Therapy.
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DOI：
10.1158/2159-8290.cd-20-1677
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发表时间：
2021-09
期刊：
影响因子：
28.2
通讯作者：
Tan K
中科院分区：
文献类型：
--
作者：
Chen GM;Chen C;Das RK;Gao P;Chen CH;Bandyopadhyay S;Ding YY;Uzun Y;Yu W;Zhu Q;Myers RM;Grupp SA;Barrett DM;Tan K
The adoptive transfer of Chimeric Antigen Receptor (CAR) T-cells represents a breakthrough in clinical oncology, yet both between- and within-patient differences in autologously-derived T-cells are a major contributor to therapy failure. In order to interrogate the molecular determinants of clinical CAR T-cell persistence, we extensively characterized the pre-manufacture T-cells of 71 patients with B-cell malignancies on trial to receive anti-CD19 CAR T-cell therapy. We performed RNA-Seq on sorted T-cell subsets from all 71 patients, followed by paired CITE-Seq and single-cell ATAC-Seq on T-cells from 6 of these patients. We found that chronic interferon signaling regulated by IRF7 was associated with poor CAR T-cell persistence across T-cell subsets, and that the TCF7 regulon not only associates with the favorable naive T-cell state, but is maintained in effector T-cells among patients with long-term CAR T-cell persistence. These findings provide key insights into the underlying molecular determinants of clinical CAR T-cell function.
