description
- "T-cell engineering strategies for Cancer therapy, either Chimeric Antigen Receptors (CARs) or TCR transfer holds promise to revolutionize cancer treatment. There are, however, considerable barriers to be overcome to take this form of therapy to a format that can benefit all EU citizens with a wide range of common cancers. The aim of this consortium is to exploit advances in T-cell engineering to allow the full potential of CAR therapy to be unleashed. At present, CAR therapy requires a bespoke autologous therapeutic product for each patient. This greatly limits practicality, scalability and commercialisation. The development of a strategy for creation of universal engineered T-cells is the first key aim of this consortium. There is an increased appreciation of the immunological hostilities (CAR) T-cells face in the tumour microenvironment, and prevention of this local immune suppressive effect will likely be critical in permitting effective tumour control. The second main aim of this proposal is therefore to engineer CAR T-cells to be resistant to the hostile microenvironment. CAR T-cells can only be effective if they can access the tumour site. Exploiting the fact that neo-angiogenesis is a hallmark of neoplastic progression, the third aim of the consortium is to utilise endothelial cues of neo-angiogenesis to direct CAR T-cell migration and activity. The central technological theme of this consortium is the application of TALEN-mediated gene editing strategies alongside genetic modification with integrating vectors. Using this approach, we will implement a clinical study of “universal” CAR T-cells in refractory lymphoma. Further, this work will be complemented with highly focused development of T-cells which are resistant to hostile microenvironments and which can home to sites of neovascularization. The legacy this consortium wishes is commercialization of universal CAR therapy for a broad swathe of human cancers."