John Gribben, M.D., DSc Barts Cancer Center of Excellence/ The London School of Medicine (United Kingdom)

IMMUNOLOGY

Targeting CLL antigens after stem cell transplantation

Update:

Our studies have focused on trying to determine why the immune system does not recognize CLL cells and lead to regression of the disease. We have used three approaches to address this question: 1) Study the CLL cells to try to find the proteins expressed on the cells that might be a target for immune cells. 2) Identify why CLL cells are poor targets for immune cells and why they are resistant to killing. 3) What is wrong with the cells of the immune system in patients with CLL?

We have made progress in our understanding of each of these. Using a serial analysis of gene expression (SAGE) array, we identified a novel protein called TOSO in CLL cells that makes these cells more resistant to killing. We have also extended our previous studies and have demonstrated why the T-cells in patients with CLL are so defective. These cells have problems in their internal machinery and cannot bring together the proteins that are essential to switch on T-cells. These defects are induced when immune cells are in contact with CLL cells, so it looks as if CLL cells have developed ways to "switch off" the immune system. We now are looking at ways to reverse this and have ongoing collaborations with investigators at MD Anderson to study this together.