Engineering T cell immunity by TCR gene transfer

T cell responses against tumor-antigens are frequently observed for some human malignancies, in particular melanoma. However, the spontaneous development of T cell responses of a sufficient strength to eradicate human malignancies is rare. The transfer of T cell receptor (TCR) __ genes into autologous T cells, a process called TCR gene transfer, allows one to engineer antigen-specific T cell responses of interest. Over the last decade, TCR gene transfer has progressed to the stage of clinical evaluation as a strategy to engineer T cell responses against tumor-antigens, in order to treat metastatic melanoma and other malignancies. The scope of the work in this thesis is to advance the development of TCR gene transfer as an engineering strategy for T cell immunity against cancer. This involves the assessment of the safety of TCR gene transfer, the evaluation of strategies to enhance the function of TCR-modified T cells in vivo, and the development of technologies to identify tumor-reactive TCR__ gene