Researchers Improve the Cancer-Killing Potential of Artificial Viruses

The finding, published today in Nature Communications, is the latest in a series of immunotherapies that attempts to unlock the immune system, deploying it against cancerous cells that, once replicating out of control, lose their virus-fighting machinery. While cancer generally elicits a mild response from the immune system, viral infections draw an aggressive immune reaction.

“We have designed a virus that has shown itself to be a potent driver of immune response,” said Doron Merkler, a professor of pathology and immunology at the University of Geneva and one of the leaders on the study. “When we compare it to other vectors, they weren’t able to trigger this kind of alarm in dependent immune response.”

What’s more, Merkler and his co-researcher Daniel Pinschewer, from the University of Basel, believe their designer virus will direct the immune system to attack not the virus, but any cell expressing a protein that is specific to cancer cells.

To do this, they engineered a virus based on the lymphocytic choriomeningitis virus (LCMV) found in rodents and humans to include a specific protein found only in cancer cells, a so-called tumor antigen. In doing this, they designed a virus that would trigger an immune response not only against virus proteins, but more specifically to the protein derived from the cancer cell, which the immune system would recognize as dangerous.

In tests carried out on mice, their immune systems released a “powerful army of cytotoxic T-lymphocytes, also known as killer cells,” according to authors. These cells successfully identified cancerous cells and destroyed them.

“The idea behind this approach is that the virus is not put into the tumor itself, but rather into secondary lymphoid organs where the immune response would be triggered,” said Merkler. “The virus is just used as a carrier to signal to the immune system that is has to respond against this protein.”

The idea of using viruses to prompt an immune response that could, in turn, trigger an attack on cancerous cells is not new. But previous attempts have had problems — namely, it is difficult to keep a virus introduced into the body from attacking healthy cells, causing an infection, or developing into a disease. And if the introduced virus is well known, the body could already have developed an immune-defense response.In 2015, the US Food and Drug Administration approved the first virus for use on cancer patients. It was shown to extend the lives of melanoma patients by an average of four and a half months and was marketed at a whopping $65,000 per treatment course. It wasn’t altogether accessible or extremely effective, but it acted as proof that cancer attacking viruses worked to some extent.

This has been a major limitation to previous developments, and it is a hurdle that the virus created in Switzerland could overcome. Because the LCMV virus is relatively rare, researchers could inject the protein-enhanced version of it intramuscularly or intravenously, rather than directly into the tumor.According to Merkler, it would function as a “strong therapeutic vaccine.”

“Most people would not have seen that virus,” said John Bell, a cancer researcher at the Ottawa Hospital Research Institute who helped to pioneer the oncological use of viruses. “For the first several infusions, you wouldn’t have an immune response against it, and it might have a leg up on other viruses.”

Thus far, no adverse effects from the virus were reported among tested animals. While it's too early to know what kind of cancers would most likely benefit from such treatment, Merkler and Pinschewer are encouraged by their results. Their next steps will include further safety testing and a search for an industrial partner that could help bring such a treatment to market.

“Of course, our hope is to eventually test this in humans,” said Merkler. “The ideal situation would be that it adds to the arsenal for medical doctors to treat and control some tumor types.”

Source: Seeker