Strategic Communication and Public Relations

Drug activates virus against cancer

No. 50 | 14/10/2013 | by Koh

Scientists from the German Cancer Research Center (DKFZ) have discovered that a drug called valproic acid increases the effectiveness of parvoviruses that are used against cancer. In some cases, pancreatic and cervical tumors that had been transplanted to rats completely regressed after treatment with a combination of the virus and an agent. The drug makes the viruses replicate more rapidly and improves their capacity to kill cancer cells.

Computer-generated representation of parvovirus H-1, Antonio Marchini, German Cancer Research Center (DKFZ)
© dkfz.de

Parvoviruses cause no harm in humans, but they can attack and kill cancer cells. Since 1992, scientists at the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) have been studying these viruses with the aim of developing a viral therapy to treat glioblastomas, a type of aggressively growing brain cancer. A clinical trial has been conducted since 2011 at the Heidelberg University Neurosurgery Hospital to test the safety of treating cancer patients with the parvovirus H-1.

“We obtained impressive results in preclinical trials with parvovirus H-1 in brain tumors,” says Dr. Antonio Marchini, a virologist at DKFZ. “However, the oncolytic effect of the viruses is weaker in other cancers. Therefore, we are searching for ways to increase the therapeutic potential of the viruses.”

In doing so, the virologists also tested valproic acid, a drug belonging to a group of drugs called HDAC inhibitors. The effect of these inhibitors is to raise the transcription of many genes that have been chemically silenced. Valproic acid is commonly used to treat epilepsy and has also proven effective in treating specific types of cancer.

The researchers initially used a combination of parvoviruses and valproic acid to treat tumor cells that had been obtained from cervical and pancreatic carcinomas and raised in the culture dish. In both types of cancer, the drug raised the rate of virus-induced cell death; in some cases, the cancer cells were even completely eliminated.

The encouraging results obtained in cultured cells were confirmed in cervical and pancreatic tumors that had been transplanted to rats. After the animals were treated with a combination of parvoviruses and valproic acid, in some cases the tumors regressed completely and animals remained free of recurrences over a one-year period. In contrast, animals treated with the same virus dose without the drug displayed no regression, not even when a 20-times higher dose of viruses was administered.

The virologists were also able to unravel the molecular mechanism by which valproic acid assists parvoviruses in fighting cancer: Treatment with the drug activates a viral protein called NS1, which is toxic. This helps the viruses replicate more rapidly and kill cancer cells more effectively.

“The synergistic effect of a combination of parvoviruses and valproic acid enables us to deliver both the viruses and the drug at low doses, which prevents severe side effects,” Marchini explains. “The results are encouraging us to carry out further tests of this combination therapy. We believe it has the potential to arrest tumor growth in severe cases of cancer.”

Junwei Li, Serena Bonifati, Georgi Hristov, Tiina Marttila, Severine Valmary-Degano,Sven Stanzel, Martina Schnölzer, Christiane Mougin, Marc Aprahamian, Svitlana P. Grekova, Zahari Raykov, Jean Rommelaere and Antonio Marchini: Synergistic combination of valproic acid and oncolytic parvovirus H-1PV as a potential therapy against cervical and pancreatic carcinomas. EMBO Molecular Medicine 2013, DOI: 10.1002/emmm.201302796

A picture for this press release is available at:
http://www.dkfz.de/de/presse/pressemitteilungen/2013/images/redVirus.jpg

Caption: Computer-generated representation of parvovirus H-1, Antonio Marchini, German Cancer Research Center (DKFZ)

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) with its more than 3,000 employees is the largest biomedical research institution in Germany. More than 1,300 scientists at the DKFZ investigate how cancer develops, identify cancer risk factors and search for new strategies to prevent people from developing cancer. They are developing new methods to diagnose tumors more precisely and treat cancer patients more successfully. The DKFZ's Cancer Information Service (KID) provides patients, interested citizens and experts with individual answers to all questions on cancer.

Jointly with partners from the university hospitals, the DKFZ operates the National Center for Tumor Diseases (NCT) in Heidelberg and Dresden, and the Hopp Children's Tumour Center KiTZ in Heidelberg. In the German Consortium for Translational Cancer Research (DKTK), one of the six German Centers for Health Research, the DKFZ maintains translational centers at seven university partner locations. NCT and DKTK sites combine excellent university medicine with the high-profile research of the DKFZ. They contribute to the endeavor of transferring promising approaches from cancer research to the clinic and thus improving the chances of cancer patients.

The DKFZ is 90 percent financed by the Federal Ministry of Education and Research and 10 percent by the state of Baden-Württemberg. The DKFZ is a member of the Helmholtz Association of German Research Centers.

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