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Jiang, Genqiao [Verfasser:in]; Neuber, Brigitte [Verfasser:in]; Hückelhoven-Krauss, Angela [Verfasser:in]; Höpken, Uta E. [Verfasser:in]; Ding, Yuntian [Verfasser:in]; Sedloev, David [Verfasser:in]; Wang, Lei [Verfasser:in]; Reichman, Avinoam [Verfasser:in]; Eberhardt, Franziska [Verfasser:in]; Wermke, Martin [Verfasser:in]; Rehm, Armin [Verfasser:in]; Müller-Tidow, Carsten [Verfasser:in]; Schmitt, Anita [Verfasser:in]; Schmitt, Michael [Verfasser:in]

In Vitro functionality and endurance of GMP-compliant point-of-care BCMA.CAR-T cells at different timepoints of cryopreservation

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  • Medientyp: E-Artikel
  • Titel: In Vitro functionality and endurance of GMP-compliant point-of-care BCMA.CAR-T cells at different timepoints of cryopreservation
  • Beteiligte: Jiang, Genqiao [Verfasser:in]; Neuber, Brigitte [Verfasser:in]; Hückelhoven-Krauss, Angela [Verfasser:in]; Höpken, Uta E. [Verfasser:in]; Ding, Yuntian [Verfasser:in]; Sedloev, David [Verfasser:in]; Wang, Lei [Verfasser:in]; Reichman, Avinoam [Verfasser:in]; Eberhardt, Franziska [Verfasser:in]; Wermke, Martin [Verfasser:in]; Rehm, Armin [Verfasser:in]; Müller-Tidow, Carsten [Verfasser:in]; Schmitt, Anita [Verfasser:in]; Schmitt, Michael [Verfasser:in]
  • Erschienen: 23 January 2024
  • Erschienen in: International journal of molecular sciences ; 25(2024), 3, Artikel-ID 1394, Seite 1-15
  • Sprache: Englisch
  • DOI: 10.3390/ijms25031394
  • Identifikator:
  • Schlagwörter: B-cell maturation antigen (BCMA) ; CAR-T cells ; multiple myeloma ; stability and function of CAR-T cells ; timepoint
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: The search for target antigens for CAR-T cell therapy against multiple myeloma defined the B-cell maturation antigen (BCMA) as an interesting candidate. Several studies with BCMA-directed CAR-T cell therapy showed promising results. Second-generation point-of-care BCMA.CAR-T cells were manufactured to be of a GMP (good manufacturing practice) standard using the CliniMACS Prodigy® device. Cytokine release in BCMA.CAR-T cells after stimulation with BCMA positive versus negative myeloma cell lines, U266/HL60, was assessed via intracellular staining and flow cytometry. The short-term cytotoxic potency of CAR-T cells was evaluated by chromium-51 release, while the long-term potency used co-culture (3 days/round) at effector/target cell ratios of 1:1 and 1:4. To evaluate the activation and exhaustion of CAR-T cells, exhaustion markers were assessed via flow cytometry. Stability was tested through a comparison of these evaluations at different timepoints: d0 as well as d + 14, d + 90 and d + 365 of cryopreservation. As results, (1) Killing efficiency of U266 cells correlated with the dose of CAR-T cells in a classical 4 h chromium-release assay. There was no significant difference after cryopreservation on different timepoints. (2) In terms of endurance of BCMA.CAR-T cell function, BCMA.CAR-T cells kept their ability to kill all tumor cells over six rounds of co-culture. (3) BCMA.CAR-T cells released high amounts of cytokines upon stimulation with tumor cells. There was no significant difference in cytokine release after cryopreservation. According to the results, BCMA.CAR-T cells manufactured under GMP conditions exerted robust and specific killing of target tumor cells with a high release of cytokines. Even after 1 year of cryopreservation, cytotoxic functions were maintained at the same level. This gives clinicians sufficient time to adjust the timepoint of BCMA.CAR-T cell application to the patient’s course of the underlying disease.
  • Zugangsstatus: Freier Zugang