Viruses versus cancer

Viruses can infect and proliferate inside cancer cells in a process known by scientists as oncolysis: "By means of this proliferation, the cancer cells are effectively killed," explains Ulrich Lauer of the Tübingen University medical clinic.

This process was first observed well over 100 years ago: "Cancer patients who were simultaneously infected with a virus often saw their tumors shrink and in some cases even disappear entirely," says Lauer. A project at the Tübingen clinic and Paul Ehrlich Institute is now looking into the efficacy of an oncolytic measles vaccination, especially created for the experiments. The project was funded by the German Education and Research ministry.

Entrance into the cell

The researchers were interested in finding ways the virus could be modified to fight cancer cells most effectively. "For the first time ever we've attempted to modify the virus so that it attacks tumor stem cells," said Lauer.

The first step in any infection is gaining entrance to the cell. "For this to happen, the virus needs a receptor, which as it were opens the door," as Lauer explained. "We were able to modify our virus in such a way that the receptor only communicated with the tumor's stem cells."

Scientists agree that stem cells control how tumors grow. These may also be the cells that grow resistant to chemotherapy, and are thus responsible for relapses. Oncolytic viruses are modified to target these cells and kill them.

Modified viruses

The viruses are altered via some deft genetic engineering - scientists are aware of the essential genetic makeup of most viruses and thus able to change it. "One of the most frequent modifications is the inclusion of a marker gene in the virus' genetic makeup," said Lauer. After the onset of the infection, marker genes are turned into marker proteins, which transmit signals that can be observed with a microscope or in a blood test. "We then know with certainty whether or not the patient is infected with the virus, the extent of the infection and how long it has been present.

The virus can also be used to deliver what are known as suicide genes. In this case, the measles virus will then be able to recognize a special receptor that is often prevalent in cancer cells. Here the virus is allowed into the cancer cell, where it proliferates and essentially forces the cell to commit suicide. A further application is the introduction of genes that stimulate the immune system against the spread of cancer cells. "All these modifications are intended to reinforce the efficiency of the viruses and to control them better," said Lauer.

The immune response is much stimulated in patients who received a measles vaccination in their childhood and are now confronted with the virus again as part of their cancer treatment. With the disintegration of cancer cells, not only viral components are released, but also very many tumor components.

This mixture has a highly stimulating effect on the immune system. However, this is not only recognized by the viral proteins, but also the proteins of the cancer cells, said Lauer. "The positive effect is the reinforcement, i.e. the stimulation of the immune system against cancer cells. If a vaccination has taken place, however, it's possible that the viral component can be caught before ever reaching the cancer cell."

Potential risks

Patients who receive oncolytic treatments have generally already undergone radiation therapy and several courses of chemotherapy. "We have yet to observe any dangers caused directly by the viral treatments," said Lauer, "but of course we are still in the initial stages of our research."

The studies currently being conducted are also testing for the potential problems of oncolytic therapy. "We have to monitor the extent to which the viruses leave the body and whether they pose a threat to the patients surroundings, including medical personnel and family members," Lauer said. "At this stage, nothing has been found, but this is being constantly monitored."

Stem cells, e.g. those responsible for the building of blood cells, have been shown to be immune to the modified measles viruses used in the Tübingen trials. This immunity, however, is defective in cancer cells, which allow the virus to gain entrance to the cells with ease. At this point scientists still believe that the oncolytic measles virus is no more harmful than any measles vaccination, a treatment that has been practised for decades.

Patients at the Tübingen clinic with inoperable peritoneal cancer have been given the treatment since April 2012. Lauer has applied a genetically modified pox vaccination directly to the abdominal cavity in the hope that the virus can quickly reach the tumor. He is convinced that oncolysis will play an important role in the future of cancer treatment.