Von Massow, Georg;
(2025)
Flaring up the Tumour: Bioprocessing Conditions and Bacterial Outer Membrane Vesicles (OMV) potentiate Gamma Delta T Cell Cancer Cell Cytotoxicity.
Doctoral thesis (Ph.D), UCL (University College London).
![[thumbnail of Von Massow_10203579_Thesis_id_removed.pdf]](https://discovery.ucl.ac.uk/style/images/fileicons/text.png) |
Text
Von Massow_10203579_Thesis_id_removed.pdf Access restricted to UCL open access staff until 1 February 2028. Download (30MB) |
Abstract
γδ T cells are immune cells that recognise a host of diseases including bacterial infections and cancer. They can show both cytotoxic as well as immunosuppressive capabilities against cancer cells. As such they have been explored as novel cancer cell therapies. Outer membrane vesicles (OMVs) are excreted from most bacteria and have been shown to activate γδ T cells in vitro. In this thesis we explore the use of OMVs loaded with Zoledronate, a known biphosphonate activator of γδ T cells, to effectively prime cancer cells for γδ T cell mediated killing. We further investigate the reprogramming of γδ T cells into induced pluripotent stem cells (iPSCs) as a platform for γδ T cell-based therapies, including the loaded OMV therapy mentioned above. We also analyse optimisation approaches for the expansion of γδ T cells, including the use of OMVs for activation as well as present a novel isolation method, aggregate strainers, for activated γδ T cells. The aggregate strainers showed a significant increase in cancer killing capacity of the γδ T cells over the cells isolated by the commonly used method, negative isolation. The reprogramming was attempted with Sendai virus and episomal vector approaches resulting in cell colony formations. Loaded-OMV priming of cancer cells significantly improved the killing in two cancer cell lines tested and were comparable to pure Zoledronate priming. OMV based expansion was less reliable than Zoledronate based expansion but produced γδ T cells with a robust killing capacity. In conclusion, we establish the functional capacity of a novel OMV based cancer therapy and describe an improved isolation approach as well as show OMVs potential in γδ T cell activation, as well as the potential to generate iPSC from γδ T cells.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Flaring up the Tumour: Bioprocessing Conditions and Bacterial Outer Membrane Vesicles (OMV) potentiate Gamma Delta T Cell Cancer Cell Cytotoxicity |
| Language: | English |
| Additional information: | Copyright © The Author 2025. Original content in this thesis is licensed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0) Licence (https://creativecommons.org/licenses/by-nc/4.0/). Any third-party copyright material present remains the property of its respective owner(s) and is licensed under its existing terms. Access may initially be restricted at the author’s request. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10203579 |
Archive Staff Only
 |
View Item |
