Generation of induced pluripotent stem cells for novel cell therapies. (360G-Wellcome-103282_Z_13_Z)

The aim of this study is to generateInduced Pluripotent Stem Cells ( iPSCs) and subsequently reprogramme these cells into mature T-cells. We aim to investigate further the use of defined T-cell populations using the following objectives: 1.To generate iPSC lrom defined human T-cell popual tions using lentiviral vectors OCT 4/SOX2/Klf4/c-MYC. (Garcia] 2 To further develop the modelshown recently that iPSC can be made from reprogrammed defined EBV-specific T-cell clones.These T-cell derived iPSC can subsequently be developed to target a specific disease process e.g.viralinfection, tumour proliferation. The purpose of this is to develop a cell therapy with the potential to treat both viral and malignant disease. (Anderson/Cobbold] 3 To assess functional competence of the T-cells which are obtained from the model in Objective 2 using both in vitro and in vivo models (Cobbold]. 4.Identify phosphopeptides present in paediatric liver tumours e.g. hepatoblastoma, hepatocellular carcinoma,and use this to target potential therapeutic options.(Cobbold] 5. Develop iPSC from tumour specific T-lymphocytes which can be differentiated into competent T-lymphocytes. (Cobbold]