The aim of this research is to exploit technology for nucleic acid delivery through the clinical testing of adoptive engineered T cells to treat cancer. Recent innovative developments in cancer gene-immunotherapy have led to very encouraging early clinical results. However, the use of engineered T cells is a challenging and complex field with further development and more proof-of-principle trials needed. This proposal builds upon previous EU funded pre-clinical projects and comprises a multidisciplinary and translational research group with wide-ranging relevant expertise. Building on encouraging clinical results targeting NY-ESO-1 in melanoma and the availability of clinical grade vector, the consortium proposes to rapidly initiate two landmark studies in this field: the first to examine the activity of engineered T cells in oesophago-gastric cancer as an example of a hard to treat common epithelial cancer; the second to undertake a randomised phase II study to determine whether an optimised cell production system developed by the partners improves the current clinical response rates in patients with metastatic melanoma treated with NY-ESO-1 targeted T-cells. Success in these trials will enable the consortia and others to carryout larger trials and potentially approval of this type of therapy as a treatment for multiple cancer types. The inclusion of a major industrial partner focused on cell therapy technology and two SMEs focus on the delivery of cell therapy will facilitate future development of this area following these trials; indeed the project also includes plans to further automate and streamline cell processing to facilitate this development. This project would enhance European expertise and competitiveness in an important emerging market. The research will also support the European biotechnology industry which will be important for the exploitation of these therapies and the successful outcome of this project.