Viruses against cancer: attack in the darknet of the immune system

For ten years after being diagnosed with bone marrow cancer, Stacy Erholtz struggled with therapies and setbacks.

In the early summer of 2013 she suffered from multiple tumors on the sternum, vertebrae and skull, but the therapy options were exhausted.

She decided to take part in a study in which she received a single maximum dose of measles vaccine virus: 10 million vaccine units - an amount that could be used to vaccinate the entire population of Baden-Württemberg.

Today it is cancer-free and has become an icon of oncolytic virotherapy.

"Stacey is living proof that virotherapy can work," says Guy Ungerechte from the National Center for Tumor Diseases (NCT) in Heidelberg.

In this form of cancer therapy, doctors use the special properties of so-called oncolytic viruses to destroy tumor cells.

Viruses are absolutely dependent on host cells for their reproduction.

Once there, they reprogram the cell machinery so that the infected cell produces several thousand copies of the virus until it bursts and perishes.

A mechanism that viruses have perfected over millennia and that researchers are now targeting against cancer cells.

On the run into the darknet

Oncolytic virotherapy is based on two mechanisms: "First, the viral infection eats its way through the tumor tissue like an avalanche, that is the direct effect," explains Ulrich Lauer, head of the virotherapy research group at the Tübingen University Clinic. Oncolysis, i.e. the dissolution of tumor cells, then activates the immune system: If an infected cancer cell bursts, a mixture of viruses, tumor cell particles and inflammatory factors is released. "That gets even the weakest immune system going," says Lauer.

Ideally, T cells, which are among the main actors in the immune system, will from now on not only recognize the infected tumor cells but also the cancer cells that have not yet been infected by the virus and destroy them. The immune system is practically restarted and programmed against the tumor. Doctors also speak of heating an immunologically "cold" tumor. "The immune-stimulating effect is one of the most important effects of virotherapy," says Unchtes, "and it works in principle in all types of tumors."

In fact, immune cells are usually able to recognize and destroy abnormal cells in the body.

"We are constantly developing tumor cells, you and I and also infants and children," explains Lauer.

However, over time and by chance, some tumor cells develop properties that enable them to escape the immune system.

“They move into the Darknet, so to speak, and can no longer be tracked down,” says Lauer.

Cancer Cell Destroyer

However, tumor cells become vulnerable to this: they are almost defenseless against viruses. Healthy cells trigger an alarm when they are attacked by viruses: They release interferons, messenger substances that shake up the immune system and ultimately ensure that the viruses are kept in check. “Cancer cells have a defective interferon system. Otherwise they would attract the attention of the immune system and end up in the cell cemetery, ”says Lauer. Viruses can therefore multiply almost unhindered in cancer cells.

The idea of ​​using viruses in the fight against cancer is not new.

More than a hundred years ago, doctors observed that canker sores sometimes disappeared as if by magic after a virus infection.

However, the first studies on cancer patients in the middle of the 20th century failed because of dangerous side effects.

At the end of the 20th century, genetic engineering opened up new possibilities.

Researchers today switch off viral genes, insert others and thus change the properties of viruses in a targeted manner.

Oncolytic viruses should, if possible, only attack cancer cells and spare healthy cells.

Some can do this naturally because they bind particularly well to certain receptors that are found in increased numbers in cancer cells.