Preparation and characterization of engineered antigen presenting cells (APCs) for the generation of cytotoxic response for transplantation-related immunotherapy.
Doctoral thesis, UCL (University College London).
Expansion and activation of cytotoxic T lymphocytes (CTL) is one of the major goals of immunotherapy but the hurdles in generating a large number of antigen-specific CTL are manifold. One of the limiting factors is the scarce availability of antigen presenting cell (APC) for T cell priming; dendritic cells (DCs) are the best APCs but their generation from adult progenitors is difficult and expensive so there is currently an active research into suitable alternatives. In this project, three different APCs models, cellular and acellular, were prepared and characterized and their potential use for clinical immunotherapy was explored. One setup was acellular, liposome-based, prepared from material currently used in in vivo applications and was tested in vitro both in human and murine settings. The other two APC systems were cellular-based; in both cases the antigen-presenting potential of a specific cord blood (CB)-derived cell population was evaluated in vitro. In the first case, a DCs-autologous responder culture was set up using whole frozen CB samples as starting material and tested in a peptide-specific model. In the second case, the antigenpresenting potential of γδ T cell in CB samples was evaluated and compared to the same population in adult, as γδ T cells have been recently shown to express antigen presentation-related markers and promote T cell proliferation in adult systems. All the three models were assessed for their practicality of preparation and use, antigen presenting capability and overall feasibility of employment in clinical settings.
|Title:||Preparation and characterization of engineered antigen presenting cells (APCs) for the generation of cytotoxic response for transplantation-related immunotherapy|
|Open access status:||An open access version is available from UCL Discovery|
|Additional information:||Copyright restricted material has been removed from the e-thesis.|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Wolfson Institute and Cancer Institute Administration > Cancer Institute > Research Department of Haematology|
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