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Title: The effects of CAMPATH on cord blood and peripheral blood cells
Author: Lee, F. Y.
ISNI:       0000 0004 5365 9917
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2015
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CAMPATH-1H is administered prior to haematopoietic stem cell transplantation (HSCT) to reduce risks of graft versus host disease (GvHD) by targeting CD52 antigens on T cells, resulting in their depletion. CAMPATH-1H is routinely used in HSCT using haematopoietic stem cells (HSC) from peripheral blood (PB) and bone marrow but not cord blood (CB). Data regarding in vivo and in vitro effects of CAMPATH-1H on immune cells is limited to PB T and B cells. Thus, we sought to determine whether a direct correlation between CD52 density and the depleting effects of CAMPATH-1H exists with fresh and frozen, resting and activated, PB and CB cells. CD52 expression was generally higher in resting CB than PB T cell subsets and B cells although CD52 levels were higher in PB natural killer cells. Furthermore, CAMPATH-1H depleted resting cells more effectively than activated cells with minimal or no necrosis. Higher percentages of apoptosis were noted in naïve CD4 and CD8 T cells with wild type/wild type genotype for caspase-8 (CASP8) gene promoter compared to donors with a single or double deletions, suggesting the potential contribution of CASP8 promoter polymorphism on sensitivity to the drug. CD52 was absent on HSC but upregulated during differentiation, implying that residual CAMPATH-1H could potentially impact on HSC differentiation by depleting CD52 expressing progenitors. This study provides evidence that low dose of CAMPATH-1H may be effective for cell depletion and prevent GvHD whilst allowing cell differentiation. Although the impacts of CAMPATH-1H on viability and differentiation of CB and PB cells were comparable, the use of CAMPATH-1H pre-CBT may not be ideal as it may further delay immune recovery and increase infection incidences. Therefore, this project provides a better understanding of CAMPATH-1H effects at the cellular and molecular level, with potential for clinical translation to achieve effective GvHD modulation while preserving GvL.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available