Frontiers in Immunology (Jan 2024)

Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time

  • Ivan Odak,
  • Lâle M. Bayir,
  • Lâle M. Bayir,
  • Lennart Riemann,
  • Lennart Riemann,
  • Ruth Sikora,
  • Ruth Sikora,
  • Jessica Schneider,
  • Jessica Schneider,
  • Yankai Xiao,
  • Nora Möhn,
  • Thomas Skripuletz,
  • Gernot Beutel,
  • Matthias Eder,
  • Arnold Ganser,
  • Reinhold Förster,
  • Christian R. Schultze-Florey,
  • Christian R. Schultze-Florey,
  • Christian Koenecke,
  • Christian Koenecke

DOI
https://doi.org/10.3389/fimmu.2024.1298598
Journal volume & issue
Vol. 15

Abstract

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Variability or stability might have an impact on treatment success and toxicity of CD19 CAR T-cells. We conducted a prospective observational study of 12 patients treated with Tisagenlecleucel for CD19+ B-cell malignancies. Using a 31-color spectral flow cytometry panel, we analyzed differentiation stages and exhaustion markers of CAR T-cell subsets prior to CAR T-cell infusion and longitudinally during 6 months of follow-up. The majority of activation markers on CAR T-cells showed stable expression patterns over time and were not associated with response to therapy or toxicity. Unsupervised cluster analysis revealed an immune signature of CAR T-cell products associated with the development of immune cell-associated neurotoxicity syndrome. Warranting validation in an independent patient cohort, in-depth phenotyping of CAR T-cell products as well as longitudinal monitoring post cell transfer might become a valuable tool to increase efficacy and safety of CAR T-cell therapy.

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