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INSPIRED Symposium Part 2: Prevention and Management of Relapse Following CAR T-cell therapy for B-ALL

Lamble, Adam J; Moskop, Amy; Pulsipher, Michael A; Maude, Shannon L; Summers, Corinne; Annesley, Colleen; Baruchel, André; ... Shah, Nirali; + view all (2023) INSPIRED Symposium Part 2: Prevention and Management of Relapse Following CAR T-cell therapy for B-ALL. Transplantation and Cellular Therapy 10.1016/j.jtct.2023.08.030. (In press).

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Abstract

While CD19-directed chimeric antigen receptor (CAR) T cell therapy for relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) has been transformative in in inducing and sustaining remission, relapse rates remain unacceptably high, with about 50% of children and young adults experiencing relapse within the first-year post-infusion. Emerging strategies to extend the durability of remission involve the use of prognostic biomarkers to identify those at high risk of relapse or incorporate strategies aimed to enhancing functional CAR T cell persistence. Nonetheless, with antigen loss/downregulation or evolution to lineage switch as major mechanisms of relapse, optimizing single antigen targeting alone is insufficient. With a focus on relapse prevention strategies, including post-infusion surveillance and treatment approaches being explored to optimize post-CAR management (e.g., combinatorial antigen targeting strategies, pre-emptive hematopoietic cell transplantation), we review the current state of the art in the prevention and management of post CAR T cell relapse. We highlight the advancements made within the field as well as identify gaps in the literature to guide future research in optimizing the prevention and management of post-CAR T cell relapses in children and young adults with B-ALL.

Type: Article
Title: INSPIRED Symposium Part 2: Prevention and Management of Relapse Following CAR T-cell therapy for B-ALL
Location: United States
DOI: 10.1016/j.jtct.2023.08.030
Publisher version: https://doi.org/10.1016/j.jtct.2023.08.030
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Chimeric antigen receptor therapy; relapse; lineage switch; immunotherapy; B-cell ALL
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10177174
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