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Post-infusion CAR T Reg cells identify patients resistant to CD19-CAR therapy
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Post-infusion CAR T Reg cells identify patients resistant to CD19-CAR therapy
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Post-infusion CAR T Reg cells identify patients resistant to CD19-CAR therapy
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Journal Article
Post-infusion CAR T Reg cells identify patients resistant to CD19-CAR therapy
2022
نظرة عامة
Approximately 60% of patients with large B cell lymphoma treated with chimeric antigen receptor (CAR) T cell therapies targeting CD19 experience disease progression, and neurotoxicity remains a challenge. Biomarkers associated with resistance and toxicity are limited. In this study, single-cell proteomic profiling of circulating CAR T cells in 32 patients treated with CD19-CAR identified that CD4
Helios
CAR T cells on day 7 after infusion are associated with progressive disease and less severe neurotoxicity. Deep profiling demonstrated that this population is non-clonal and manifests hallmark features of T regulatory (T
) cells. Validation cohort analysis upheld the link between higher CAR T
cells with clinical progression and less severe neurotoxicity. A model combining expansion of this subset with lactate dehydrogenase levels, as a surrogate for tumor burden, was superior for predicting durable clinical response compared to models relying on each feature alone. These data credential CAR T
cell expansion as a novel biomarker of response and toxicity after CAR T cell therapy and raise the prospect that this subset may regulate CAR T cell responses in humans.
