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Improving CAR T cell immunotherapy–mediated remissions for pediatric leukemia
David M. Barrett
David M. Barrett
Published April 15, 2019
Citation Information: J Clin Invest. 2019;129(5):1842-1844. https://doi.org/10.1172/JCI128743.
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Commentary

Improving CAR T cell immunotherapy–mediated remissions for pediatric leukemia

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Abstract

Chimeric antigen receptor (CAR) T cells are an effective therapy for relapsed or refractory pediatric B cell leukemia. Analysis of the starting material, the T cells collected from the patient prior to CAR manufacture, reveals possible biomarkers of cells destined to perform poorly in patients. Long-term follow-up shows that long periods of B cell aplasia, a marker of in vivo CAR activity, are associated with longer remission but also a higher chance of antigen-negative relapse. The role of transplantation as consolidative therapy is unclear in this nonrandomized data, but clearly warrants further study.

Authors

David M. Barrett

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Figure 1

Model of the factors influencing CAR T cell response and persistence.

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Model of the factors influencing CAR T cell response and persistence.
T ...
T cell intrinsic factors including the CD4/CD8 ratio, memory phenotype, expression of exhaustion markers, and metabolic profile can inform how the cells are supported in the lab during CAR manufacture. Standard assessments of CAR T cell function such as cytokine release and polyfunctional index will be important for comparison across trials. Leukemia intrinsic factors such as driver lesion (cytogenetic, fusion, or mutation), preexisting antigen-low clones, and overall antigen burden will inform relapse risk. After infusion, patient monitoring with CAR T cell proliferation area under the curve (AUC), duration of BCA, and assessment with ultrasensitive next-generation sequencing (NGS) MRD will inform the ultimate decision for post–CAR consolidation, such as use of allogeneic transplantation.

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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