Physicians receive Pfizer Prize for research on leukemia, cardiac arrhythmias

This year, four of a total of fifteen Pfizer Research Prizes have been awarded to physicians from the University of Bern and the Inselspital, University Hospital Bern. The award-winning work deals with leukemia, cardiac arrhythmias and the fever threshold in children and adolescents with cancer.

The Pfizer Research Prize is one of the most important research prizes for medicine in Switzerland. It is awarded annually to outstanding young scientists who have made outstanding and pioneering contributions to laboratory or clinical research at Swiss research institutes or hospitals.

The Pfizer Research Prize is awarded at the request of independent scientific committees in five fields, and the prizes are each worth 15,000 Swiss francs. In the field of oncology, Ass. Prof. Dr. Carsten Riether of the Department for BioMedical Research (DBMR) of the University of Bern and University Clinic for Medical Oncology at Inselspital will receive the award. PD Dr. med. Jin Li, Institute of Biochemistry and Molecular Medicine (IBMM), and PD Dr. Ange Maguy, Department of Physiology at the University of Bern, will each receive the award in the fields of cardiovascular medicine, urology and nephrology.

In the field of pediatrics, Dr. med. Christa König of the University Clinic of Pediatrics at Inselspital and Medical Faculty member of the University of Bern will receive an award.

I am very pleased about this success. The Pfizer Research Prizes are an important recognition - also for the strong commitment of our faculty to the promotion of young researchers."

Dr med. Claudio Bassetti, Professor and Dean of Faculty of Medicine, University of Bern

Combating therapy resistance in blood cancer

Acute myeloid leukemia is a malignant disease of the hematopoietic (blood cell formation) system that occurs mainly in people over 65 and originates in leukemia stem cells.

Due to naturally accompanying symptoms and a poor general condition, the affected age group often cannot be treated with intensive chemotherapy or possible stem cell transplantation. They would only be able to be treated with so-called hypomethylating agents, which are special drugs that support blood formation. However, leukemia stem cells are resistant to these substances.

Carsten Riether and his team found that the surface molecule CD70 is produced at higher levels by leukemia stem cells during treatment with hypomethylating agents. Consequently, the team determined whether it would be possible to target CD70 with an antibody and thus improve the success of treatment.

Leukemia stem cells were significantly reduced as a consequence of combating CD70 with antibodies in pre-clincal models and in a phase I clinical trial. "This study has discovered a new mechanism for resistance to therapy and has facilitated the investigation of a potential treatment strategy", Riether explains.

Stabilizing the cardiac rhythm

Every contraction of the heart muscle is preceded by electrical stimulation. For this to happen, the electrical activity must be correctly mediated by the cells of the heart. Patients with long QT syndrome have a defective ion channel, a protein on the surface of heart cells coordinating the electrical activity.

The time for the heart to recharge between each heartbeat (the so-called QT time) is abnormally prolonged and puts patients at risk of life-threatening arrhythmias and sudden cardiac arrest. Currently available treatment options are nonspecific and fail to correct the underlying physiology.

PD Dr. Ange Maguy and PD Dr. med. Jin Li identified an antibody targeting a specific ion channel that is able to restore the electrical stability in heart cells of a patient with long QT syndrome. "Moreover, these antibodies completely suppressed the occurrence of arrhythmias in the heart cells of a patient with long QT syndrome", says Jin Li. "This is the first study to implement the use of antibodies for the treatment of cardiac arrhythmias", adds Ange Maguy.

New fever threshold for children and adolescents with cancer

The most common side effect of chemotherapy in children and adolescents with cancer is fever with a temporary shortage of defending white blood cells, a condition called neutropenia (FN). FN is treated with emergency hospitalization and immediate administration of antibiotics, but it is unclear at what fever threshold this therapy must be initiated.

The team around Christa König of the University Clinic of Pediatrics at Inselspital and Cécile Adam of the University Hospital of Lausanne has investigated if a higher fever threshold (ear temperature 39.0°C) is not worse for the diagnosis of FN than a lower fever threshold (38.5°C) in terms of safety.

This first study worldwide on the fever threshold in FN was conducted at six Swiss pediatric oncology centers. 269 children and adolescents were involved. "Our results show that the higher fever threshold of 39.0°C is no less safe. By switching to the higher temperature, clinics can reduce overtreatment in the future," explains Christa König. This influences individual patient management and has additional public health economic implications.