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Title: Epstein-Barr virus associated diseases : immunotherapy and cytokine gene expression
Author: Asghar, Mobin
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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The aim of the first study was to use the SCID model to investigate the effect of varying doses of human unmanipulated peripheral blood mononuclear cells (PBMC), polyclonal and EBV peptide-specific cytotoxic T cell lines (CTL) on outgrowth and therapy of autologous LCL tumours. Effector cells were mixed with fixed tumorigenic dose of autologous LCL cells at varying ratios and injected s/c into SCID mice. Unmanipulated PBMC failed to control the outgrowth of LCL tumours. Polyclonal CTLs prevented tumour outgrowth down to the CTL:LCL ratio of 0.25:1 suggesting that outgrowth of EBV-positive tumours is effectively controlled by autologous EBV-specific CTLs. Polyclonal CTLs also improved survival of SCID mice with already established autologous LCL tumours. Positive effect of CTL on survival and tumour mass reduction was greater in animals with small tumour mass at start of therapy as compared to those with larger tumours. Delivery of multiple CTL infusions via the intravenous (I/V) route was more effective in reducing tumour mass than injection of a single fixed doses via the I/V or intratumour route. In contrast, only the EBV peptide-specific CTLs with a higher frequency of detectable precursors in the peripheral blood prevented tumour outgrowth below CTL:LCL ratio of 1:1. Peptide-specific CTLs targeting an immunodominant LMP1 epitope also successfully controlled outgrowth of LCL tumours below CTL:LCL ratio of 1:1, suggesting the possible extension of CTL therapy to EBV positive malignancies with restricted EBV gene expression patterns. The second study investigated the cytokine gene expression pattern of EBV associated diseases. Dysregulation of the cytokine network has been proposed as a cofactor in pathogenesis of EBV related conditions. Higher level of cytokine gene expression has been found in lymphoid tissue of patients with IM as compared to normal individuals and in cases of EBV positive PTLD, HD and NPC as compared to EBV negative cases.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available