AUTHOR=Odak Ivan , Bayir Lâle M. , Riemann Lennart , Sikora Ruth , Schneider Jessica , Xiao Yankai , Möhn Nora , Skripuletz Thomas , Beutel Gernot , Eder Matthias , Ganser Arnold , Förster Reinhold , Schultze-Florey Christian R. , Koenecke Christian TITLE=Brief research report: in-depth immunophenotyping reveals stability of CD19 CAR T-cells over time JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1298598 DOI=10.3389/fimmu.2024.1298598 ISSN=1664-3224 ABSTRACT=

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.