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 language | English |
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Qualification | PhD |
Awarding Institution |
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Supervisors/Advisors |
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Award date | 1 Jul 2024 |
Print ISBNs | 9789465060927 |
DOIs | |
Publication status | Published - 1 Jul 2024 |