On the TRAIL of a killer: mechanisms of action of an allogeneic NK cell therapy

Amanda Antoinette van Vliet

    Research output: PhD ThesisPhD-Thesis - Research and graduation internal

    480 Downloads (Pure)

    Abstract

    Natural killer (NK) cell therapy is becoming more and more attractive as a treatment option for various types of cancer due to its high safety profile and proven clinical efficacy. Currently, different sources (e.g. peripheral blood NK (PBNK), umbilical cord blood NK (UCB-NK), hematopoietic stem cells (HSCs), cell lines, induced pluripotent stem cells (iPSCs)) and different culture strategies (e.g. feeder cell-based, cytokines) are being investigated to attain optimal expansion, genetic manipulation and high functionality. It is worth mentioning that the choice of source or culture method can significantly impact the efficacy and characteristics of a cell product. In addition, depending on the starting source, the manufacturing workflow requires different process pipelines. Glycostem has established a platform for a good manufacturing practice (GMP) grade off-the-shelf cryopreserved NK cell product using CD34+ HSCs from UCB. The NK cell product GTA002 is currently tested in a phase I/IIa clinical trial in patients with acute myeloid leukemia (AML). To further improve the product and extend its therapeutical applications, a comprehensive understanding of its characteristics and mechanisms of action is crucial, which is addressed in this thesis from various perspectives. In various solid indications, the activation mechanisms of GTA002 were investigated (Chapter 3-4), characteristics of NK cell batches with high cytotoxic potential were identified (Chapter 4), the synergy of combination therapy was explored (Chapter 5), and the immunomodulatory role of GTA002 was studied (Chapter 6-7).
    Original languageEnglish
    QualificationPhD
    Awarding Institution
    • Vrije Universiteit Amsterdam
    Supervisors/Advisors
    • de Gruijl, Tanja, Supervisor, -
    • Gibbs, Sue, Supervisor, -
    • Spanholtz, J., Co-supervisor, -
    • Georgoudaki, A.M., Co-supervisor, -
    Award date1 Jul 2024
    Print ISBNs9789465060927
    DOIs
    Publication statusPublished - 1 Jul 2024

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