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Title:
Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients | Nature Cancer
Description:
Low-affinity CD19 chimeric antigen receptor (CAR) T cells display enhanced expansion and persistence, enabling fate tracking through integration site analysis. Here we show that integration sites from early (1 month) and late (>3 yr) timepoints cluster separately, suggesting different clonal contribution to early responses and prolonged anti-leukemic surveillance. CAR T central and effector memory cells in patients with long-term persistence remained highly polyclonal, whereas diversity dropped rapidly in patients with limited CAR T persistence. Analysis of shared integrants between the CAR T cell product and post-infusion demonstrated that, despite their low frequency, T memory stem cell clones in the product contributed substantially to the circulating CAR T cell pools, during both early expansion and long-term persistence. Our data may help identify patients at risk of early loss of CAR T cells and highlight the critical role of T memory stem cells both in mediating early anti-leukemic responses and in long-term surveillance by CAR T cells. Amrolia and colleagues characterize the clonal origins of long-term persistent CAR T cells from the CARPALL trial using low-affinity CAR T cells mediating long-term anti-leukemic control in patients through TSCM-mediated responses.
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nature portfolio journals permissions reprints gene editing technology nature portfolio privacy policy ebv-specific t-cell infusions advertising shannon diversity index low-affinity cd19 car single-cell transcriptional profiling social media nihr research professorship prolonged anti-leukemic surveillance chimeric antigen receptor-modified nature https decade-long leukaemia remissions b-cell lymphoblastic leukemia acute lymphoblastic leukaemia steady-state reconstitution phases author information authors nature+ nature chimeric antigen receptor cd62l+cd45ra+cd95 expression university college london chimeric antigen receptors dana farber/boston children dana-farber/boston children extended data fig source data fig chronic lymphocytic leukemia supplementary information section permissions author correspondence springerlink instant access bilyana popova andre lopes long-term surveillance memory stem cells institutional subscriptions read long-term outcome gene therapy program cell immunological memory long-term persistence c1qb-expressing macrophages privacy treat leukemia remission author gene content long-term car
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headline:Clonal expansion of T memory stem cells determines early anti-leukemic responses and long-term CAR T cell persistence in patients
description:Low-affinity CD19 chimeric antigen receptor (CAR) T cells display enhanced expansion and persistence, enabling fate tracking through integration site analysis. Here we show that integration sites from early (1âmonth) and late (>3âyr) timepoints cluster separately, suggesting different clonal contribution to early responses and prolonged anti-leukemic surveillance. CAR T central and effector memory cells in patients with long-term persistence remained highly polyclonal, whereas diversity dropped rapidly in patients with limited CAR T persistence. Analysis of shared integrants between the CAR T cell product and post-infusion demonstrated that, despite their low frequency, T memory stem cell clones in the product contributed substantially to the circulating CAR T cell pools, during both early expansion and long-term persistence. Our data may help identify patients at risk of early loss of CAR T cells and highlight the critical role of T memory stem cells both in mediating early anti-leukemic responses and in long-term surveillance by CAR T cells. Amrolia and colleagues characterize the clonal origins of long-term persistent CAR T cells from the CARPALL trial using low-affinity CAR T cells mediating long-term anti-leukemic control in patients through TSCM-mediated responses.
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Cancer immunotherapy
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