Up to 10% of patients with CLL and SLL may develop a type of lymphoma which is known as Richter’s Transformation. It is unclear whether this may be due to changes in the original CLL cells or if it is caused by the development of a completely new lymphoma. Epstein-Barr virus (EBV), which also causes mononucleosis (the kissing disease), has been a suspected instigator for the transformation, but this has not been conclusively shown.
Determined to find an answer, Dr. Helen Heslop (Baylor College of Medicine) has been assessing whether EBV is involved in Richter’s. EBV produces proteins, and Dr. Heslop examined whether those proteins are consistently found in patients with Richter’s. She also tested the samples for other proteins which are not EBV-associated. The premise is to define exactly which proteins are most commonly expressed in Richter’s. In six samples tested there was only evidence of EBV in 2 samples. In contrast, CLL cells from all six samples expressed very high levels of proteins called SURVIVIN and PRAME.
The plan is to now develop a therapy to specifically target these proteins using killer T-cells (a type of immune cell which attacks antigens such as viruses and bacteria). Dr. Heslop and colleagues at Baylor have used a similar approach to treat patients with other types of lymphoma. The clinical responses were encouraging, so she proposed to develop a similar, customized therapy for CLL patients with Richter’s.
Dr. Heslop has tested whether she can grow killer T-cells targeting the culprit proteins in the laboratory. This proved successful. Now she will take this work forward and develop a clinical trial for Richter’s patients. The T-cells will be customized to target the proteins SURVIVIN and PRAME and the EBV proteins. By targeting this combination of proteins, all patients with Richter’s can hopefully be effectively treated.
