Current research to overcome T-cell dysfunction in CLL and improve therapies

Arnon Kater, MD, PhD of the Academic Medical Center, Amsterdam, Netherlands talks about current research to overcome T-cell dysfunction in chronic lymphocytic leukemia (CLL) at the 2016 International Workshop of the German CLL Study Group (GCLLSG) in Cologne, Germany. He begins by explaining that in CLL research, there is an interest in T-cell function. With kinase inhibitors you can postpone the disease and treat patients for a long time. However, there are two problems. Firstly, patients will not be cured. Secondly, it is unaffordable to treat patients indefinitely. Therefore, it is important to come up with a better approach. The history of CLL shows that the only way to cure patients is by giving an allogeneic stem cell transplantation. This shows that a T-cell mediated response to leukemia cells is a feasible. The only problem is that taking allogeneic cells is extremely toxic, especially for the elderly population. He points out that nowadays it is possible to use autologous T-cells in many types of cancers. However, results with these therapies have so far been poor in CLL. This is because the T-cells have an acquired dysfunction. Prof. Kater explains that a lot of his research is underway to investigate why this happens in CLL and what needs to be done to overcome this. One of the methods is by looking at virus-specific T-cells in CLL. Also, there are now some very preliminary clues that the metabolism in those T-cells are disturbed; they have a different way of using energy. He explains that if this T-cell dysfunction can be repaired, therapies such as CAR T-cell or checkpoint inhibitors, can be much more efficient.

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