Forcing the Immune System to Attack Cancer

With a floor-length list of side effects and the uncertainty of whether chemotherapy and radiation will work, patients are turning to treatments that harness the body’s own immune system to fight cancer.

Immunotherapy has achieved spectacular results in some instances, yet it is effective for only about half the patients who try it. The other half simply do not respond.

Tackling this issue head on, Swiss researchers from the University of Geneva and the University of Basel have created a new, vigorous “designer virus” that might help the immune system find and kill cancer cells once and for all.

The main reason the human body is unable to fight cancer is because it cannot recognize it. This is because cancer cells consist of the patient’s own DNA, which the body’s immune system recognizes as natural. A third-party agent foreign to the body, such as a virus, could unmask those seemingly normal cancer cells, helping the immune system to find and attack them using the immune system’s own T-cells.

Yet immunotherapy can fail. The Cancer Treatment Centers of America, for example, states that the T-cells may be exhausted and not numerous enough to overcome the cancer. Another theory holds that the body does not have enough neoantigens, molecules that attach onto cancer cells during immunotherapy treatment and alert the immune system of their location. It is as if the phone is ringing and no one is answering.

The Swiss designer virus was created to overcome that problem. It incites such an extreme response in the immune system, T-cells have no choice but to pick up the phone and fight back.

The researchers started with lymphocytic choriomeningitis, a virus that is extremely common, especially in mice. In fact, about 50 percent carry the virus, which can also infect humans. Daniel Pinschewer, senior author of the study published in Nature Communications and professor at the Department of Biomedicine at the University of Basel, said the virus is the perfect agent because it has few side effects. The symptoms of LCMV are a low-grade fever for a few days and nausea or headache.

“It’s mostly totally benign, it’s like the common cold,” Pinschewer said. “So, if you have cancer you might make the choice. Can you accept the discomfort of the virus if it will help you?”

Pinschewer made the virus suitable for immunotherapy by attaching a protein unique to the patient’s particular type of cancer to the virus. The immune system’s T-cells then read the cancer as part of the virus, alerting an immune response that seeks and destroys the cancerous cells.

“It is very important to note that the virus doesn’t have to get into the cancer,” Pinschewer explained. “It only has to get to the immune system or the body’s ‘defense system,’ which has its ‘training camps’ in the lymph nodes and spleen. That’s where our ‘soldiers,’ our T-cells, are educated, and it’s the soldiers that will patrol the body and seek and destroy the tumors.”

There is also a possibility that multiple strains of the virus carrying different types of proteins could help a person whose cancer has mutated and metastasized in other parts of the body.

Moreover, because viruses can lie dormant in the body for years after infection, this particular immunotherapy might provide long-lasting protection, igniting an immune response whenever the cancer recurs. Still, this is of “secondary importance” to eradicating a person’s existing cancer, Pinschewer said.

The success of the virus depends on success in human trials, which is the next phase for Pinschewer and his team. He expects to see a strong response rate, since the designer virus has been very successful in animal testing. He hopes that the first patients will begin treatments within the next two years.

“As scientists we have to be modest until something has proven it works,” Pinschewer said. “I’m not making any promises. But, what makes our mouse study interesting is that there is a mechanism that we have not [previously] leveraged to make active immunization principles work against cancers. So it encourages me to think that we have a real chance of making this long dream work out.”

Cassie Kelly is an independent technical writer.