Kirtsios, Efstratios;
(2024)
Investigating the molecular impact of dual antigen targeting with CD19\CD22 chimeric antigen receptor (CAR) T-cells.
Doctoral thesis (Ph.D), UCL (University College London).
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Abstract
Cancer remains one of the most life-threatening health conditions. Identifying cancer's weaknesses can be exploited to design treatments; decades of research show that the patient’s immune system is well-equipped to exploit cancer-specific vulnerabilities and kill cancer cells, but not always effectively. Immunotherapy gives the immune system a helping hand by boosting its ability to recognise cancer cells and mediate their killing. One such approach is ‘Autologous CAR-T Therapy,’ which utilizes T-lymphocytes extracted from the patient, genetically modified to express one or more artificial Chimeric Antigen Receptors (CARs), and re-infused into the patient. The CAR enables T-lymphocytes to specifically recognise, and target cancer cells based on unique molecular surface markers, akin to a key designed to fit a specific lock. Although this approach has yielded life-saving results, challenges remain when cancer cells alter these markers or when CAR T-lymphocytes fail to persist in the bloodstream. Our team hypothesized that genetic enhancement by incorporating one or more CARs could influence the natural biology of T-lymphocytes. Thus, we aim to dissect the differences between T-lymphocytes carrying one or more CARs by analysing their transcriptomic and cell surface profiles using CITE-seq, Flow Cytometry and DNA-PAINT Super-Resolution Imaging. Results from this work may result in directing the scientific community to refine CAR-T therapeutic strategies to better eradicate blood cancer and benefit more patients.
| Type: | Thesis (Doctoral) |
|---|---|
| Qualification: | Ph.D |
| Title: | Investigating the molecular impact of dual antigen targeting with CD19\CD22 chimeric antigen receptor (CAR) T-cells |
| Language: | English |
| Additional information: | Copyright © The Author 2024. 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 > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10200154 |
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