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Comprehensive Cancer Center Freiburg - CCCF

Stuttgart, 05/03/2022

Prevention Award for Professor Robert Zeiser

Cancer drug azacitidine could prevent relapses in leukemia therapy


May 3, 2022

Professor Robert Zeiser, MD, of the Department of Internal Medicine I at Freiburg University Hospital, received the Prevention Award for his cancer research at the 128th Congress of Internal Medicine. He shares the prize with Professor Martin Heni, MD, of the University of Tübingen, who conducts research on diabetes. Informationsdienst Wissenschaft (idw) writes on 02.05.2022:

"Professor Robert Zeiser, MD, is researching CAR-T cell therapy for the treatment of leukemia. The aim of the therapy is to strengthen the body's own defense against cancer. For this purpose, defense cells are taken from the blood and equipped with a chimeric antigen receptor (CAR) in the laboratory. The CAR shows the T cells how to find the leukemia cells after infusion. In acute myeloid leukemia (AML), a blood cancer that occurs primarily in older people, the T cells recognize a specific protein called CD123 on the surface of the cancer cells. Until now, CAR-T cell therapy has not been sufficiently effective in AML because the cancer cells produce only a small amount of CD123 and the number of CAR-T cells declines over time. This led to a loss of efficacy and relapse of AML in patients.

One way out could be pretreatment with azacitidine. The drug had been discovered in the 1960s in the bacterium Streptoverticillium ladakanus. It was subsequently used for a long time as a cytostatic drug to treat leukemias. In 2004, azacitidine was newly approved in the United States and later in Europe. It is considered one of the first agents to interfere with epigenetic regulation by removing methyl groups from DNA, thereby activating genes and promoting the formation of the protein CD123. "Professor Zeiser was able to show in a mouse model that pretreatment with azacitidine stimulates the formation of CD123 on cancer cells," explains Professor Stefan Frantz, MD, chairman of the German Foundation for Internal Medicine. This could enhance the effect of the cancer therapy. A second effect of the treatment was the increased appearance of so-called CTLA-4 negative CAR T cells. This prevents premature depletion of CAR T cells, which help kill leukemia cells."

(...) "The German Foundation for Internal Medicine, together with the German Society for Internal Medicine, awards the Prevention Prize for the best paper submitted from German-speaking countries in German or English in the field of primary and secondary prevention of internal diseases. The prize is worth 10,000 euros and will be split between the two winners in 2022."

Original publication in Nature Communications 2021; 12:6436


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