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Title: Augmentation of the immunogenicity of acute lymphoblastic leukaemia in vitro
Author: Lee, Andrew John
Awarding Body: University of Leicester
Current Institution: University of Leicester
Date of Award: 2000
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Acute lymphoblastic leukaemia (ALL) is a heterogeneous disease of different immuno-phenotypically defined subtypes. Although successful conventional therapies are available, for a proportion of patients (approximately 30%) these are ultimately unsuccessful. ALL relapse is a result of the failure of the immune system to recognise these malignant cells and down regulation of crucial molecules required for cognate CD4+ T-cell recognition has been postulated as a means of immune escape. This study has concentrated on the augmentation of the immunogenicity of B-cell ALL to facilitate the generation of an anti-leukaemic immune response. The initial gene therapy approach to enhancing ALL immunogenicity relied upon the successful transfection of primary ALL cells with a range of constructs carrying immunomodulatory genes, and the development of a protocol to routinely establish ALL cell lines from primary cultures, thus enabling the use of 'low-yield' transfection systems to introduce recombinant DNA into ALL cells. This study was however unable to develop methodology to develop methodology to either transfect the ALL cells or to establish such cell lines in culture. This study does however demonstrate the effectiveness of physiological augmentation of ALL immunogenicity, showing that the CD154+ cell line, 40L.1, induces the upregulation of the expression of a number of crucial molecules involved in antigen recognition. The activation of ALL cells resulting from coculture with the 40L.1 cell line enhances allogeneic and autologous MLR responses to CD40-activated ALL cells and also induces CTL effectors which are capable of lysing wild-type autologous ALL cells. It is therefore conceivable that CD40-mediated activation of ALL could generate an active anti-tumour response in patients, following conventional therapy, reducing the incidence of relapse.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available