Ordidge, KL; (2014) In vivo assessment of a novel dual cell cancer therapy using conventional and novel cell tracking methods. Doctoral thesis , UCL (University College London).

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Abstract

Adoptive immunotherapy for cancer is a rapidly expanding field. Along with new techniques and technologies for cell engineering comes a pressing clinical need to discover the location of these cells after injection and to quantify the number of cells in a particular location. The use of agents to enhance tissue contrast is crucial to improve the ability of imaging techniques to distinguish cells from background signal, in order to track cells in vivo. Human donor T cells were transduced to express a tumour antigen specific T cell receptor. Transduced T cells were labeled with novel and conventional radiolabels for in vivo tracking using a combined single photon emission computed tomography and computed tomography (SPECT/CT) scanner. Transduced T cells were used in combination with TRAIL-expressing MSCs to produce a novel dual cell anti-cancer therapy in an in vivo lung metastases cancer model. The data in this thesis demonstrates that a novel tri-functional probe designed for long-term cell tracking, whilst resulting in superior cell labeling and retained activity over time compared with conventional methods, causes significant cell toxicity. It also demonstrates, for the first time, that a tumour antigen specific T cell therapy can be effective against lung metastases, leading to a significant reduction in tumour burden. These engineered T cells combined with MSC TRAIL also significantly reduce metastatic tumour burden, although there was no significant benefit to using the dual cell therapy.

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