Bioengineered T cells for Leukaemia and Lymphoma

Sammanfattning: Cancer immunotherapy is a promising tool for treatment of malignancies. However, there are still hindrances that need to be overcome. Chimeric antigen receptors have the ability to direct immune cytotoxic cells towards tumour-associated antigens in major histocompatibility complex-independent manner. In this study 2 generations of such receptor-bearing T cells, against the CD19 B-cell marker, were investigated for treatment of chronic lymphocytic leukaemia. The 2 nd generation   of this genetically engineered T cell contains CD3ζ  and CD28 intracellular domain, while the third generation has CD137 (4-1BB) in addition. Previous studies have demonstrated advantages of 2 nd  generation chimeric antigen receptor T cells  compared with 1 st generation. In this project the 2 nd and 3 rd generation T   cells  were compared for transduction efficiency, phenotype, proliferative capacity and cytotoxicity in response to antigen from a malignant B cell line. The analysis of transduction showed similar transduction efficiency for both types of chimeric  antigen receptor. However, the data from T cell phenotyping and cytotoxic analysis could not be used for drawing any conclusion, because of too little amount of samples and subsequently, lack of statistical analysis. Further, the proliferative capacity was similar between all transduced T-cell groups and did not give any   conclusive data. The next step will be to stimulate the 2 nd and 3 rd generation T cells with autologous target cells and follow them for a longer time since  allogeneic tumour cell lines trigger an alloreactivity that may mask the different activation states that may occur in the two T cell products.