Use this URL to cite or link to this record in EThOS: https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.798449
Title: CD20 as a prognostic biomarker and as a potential therapeutic target of oncolytic measles virus in adult acute lymphoblastic leukaemia
Author: Bailey, Katharine Elizabeth
ISNI:       0000 0004 8507 5043
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2019
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Abstract:
Adult acute lymphoblastic leukaemia (ALL) is an aggressive haematological malignancy with a poor outcome for 50% of patients. CD20 is an important target antigen in ALL. I have examined the role of CD20 as a biomarker in ALL and investigated whether an oncolytic measles virus (MV) targeted to CD20 is therapeutically relevant. In Chapter 3, I analysed CD20 expression in primary specimens from the UKALL14 trial. Increasing CD20 expression ‐ whether measured by the percentage of positive ALL cells or as CD20 antigen density ‐ conferred inferior survival. I developed a RT‐qPCR assay to quantify the gene expression of CD20 for use in specimens without stored cells. This correlated well with the flow cytometry data with a similar relationship to outcome. ALL cells are known to be sensitive to MV oncolysis. Chapter 4 of my thesis investigated the therapeutic potential of a MV genetically modified to target entry via CD20. MVHCD20 was more effective than the native MV at killing CD20 positive cells in vitro. A MV 'blinded' to the native MV receptors by ablation of the residues necessary for receptor‐binding also demonstrated efficacy suggesting it would have therapeutic efficacy whilst avoiding offtarget effects. In Chapter 5 I investigated the underlying mechanism of the MV oncolysis previously demonstrated. Neutrophils are effector cells in MV‐oncolysis but not by antibody dependent cellular cytotoxicity, as previously shown by my lab, so I explored their role in antibody‐mediated phagocytosis after CD20 targeted MV infection of ALL cells. I demonstrated that true phagocytosis was a rare event. However, neutrophils demonstrated an antibody‐dependent cellular process called 'trogocytosis'. Trogocytosis did not result in target cell death, however it appeared to increase neutrophil activation, which suggests that activated neutrophils may orchestrate additional immune responses following MV oncolysis.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.798449  DOI: Not available
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