Overcoming drug resistance in CLL

Lead researcher - Dr Stephen Beers, University of Southampton
Understanding the regulation of antibody therapy by NOTCH1 mutations in CLL
Amount awarded: £230,912
Award start date: 01 Aug 2015
Award duration: 3 years

CLL is the most common adult leukaemia in the Western world.  It is a slowly progressing disease where the bone marrow produces too many white blood cells (lymphocytes). As the condition develops, patients experience life-threatening symptoms due to the weakened immune system. Despite the advances in treatment, CLL remains incurable, greatly diminishing sufferer’s quality of life and putting a tremendous burden on families and the public health service.
Combining conventional anti-cancer chemotherapy drugs with new immunotherapy treatments (antibodies) has shown promising results. Antibodies like rituximab represent an exciting new type of treatment for cancers. Unfortunately, some tumours with a specific DNA sequence alteration (mutation) in a gene called NOTCH1 are resistant to rituximab treatment. Using primary clinical samples, bespoke assays of antibody activity and sophisticated pre-clinical models we aim to discover the underlying mechanisms of this resistance, and investigate possibilities for reversing them, allowing us to design better treatment strategies for lymphoma and leukaemia patients in the future.