RESUMO
In the context of relapsed and refractory childhood pre-B cell acute lymphoblastic leukemia (R/R B-ALL), CD19-targeting chimeric antigen receptor (CAR)-T cells often induce durable remissions, which requires the persistence of CAR-T cells. In this study, we systematically analyzed CD19 CAR-T cells of 10 children with R/R B-ALL enrolled in the CARPALL trial via high-throughput single-cell gene expression and T cell receptor sequencing of infusion products and serial blood and bone marrow samples up to 5 years after infusion. We show that long-lived CAR-T cells developed a CD4/CD8 double-negative phenotype with an exhausted-like memory state and distinct transcriptional signature. This persistence signature was dominant among circulating CAR-T cells in all children with a long-lived treatment response for which sequencing data were sufficient (4/4, 100%). The signature was also present across T cell subsets and clonotypes, indicating that persisting CAR-T cells converge transcriptionally. This persistence signature was also detected in two adult patients with chronic lymphocytic leukemia with decade-long remissions who received a different CD19 CAR-T cell product. Examination of single T cell transcriptomes from a wide range of healthy and diseased tissues across children and adults indicated that the persistence signature may be specific to long-lived CAR-T cells. These findings raise the possibility that a universal transcriptional signature of clinically effective, persistent CD19 CAR-T cells exists.
Assuntos
Leucemia Linfocítica Crônica de Células B , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Antígenos CD19/genética , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Receptores de Antígenos de Linfócitos T , Indução de Remissão , Linfócitos TRESUMO
BACKGROUND: The concept of self-efficacy has been proposed as a suitable outcome measure in psychiatry. Self-efficacy refers to an individual's belief that he or she can control important aspects of his or her life. An audit of 67 consecutive clients attending an acute psychiatric day unit was conducted, measuring self-efficacy at admission to the unit and at discharge. CONCLUSION: The concept of self-efficacy was easily explained to clients, and was measured using a 15-point questionnaire. Self-efficacy increased following treatment in the day unit, and this increase appears to reflect an underlying change in the individual's self-belief.