Using two different viruses to fight tumors

An international research group led by the University of Basel has developed a promising strategy for therapeutic cancer vaccines. Using two different viruses as vehicles, they delivered specific tumor components in experiments on mice with cancer to stimulate their immune systems to attack the tumor. The approach is currently being tested in clinical studies.

The use of the immune system as an ally in the fight against cancer forms the basis of a wide range of modern cancer therapies. One of them is therapeutic cancer vaccination: after diagnosis, specialists set out to determine which components of the tumor might function as an identifying feature of the immune system. The patient then receives exactly these components by vaccination, in order to trigger the strongest possible immune response against the tumor.

Viruses that have been rendered harmless are used as vehicles to deliver characteristic tumor molecules into the body. In the past, however, many attempts to create this type of cancer treatment have failed due to an insufficient immune response. One of the obstacles is that the tumor is made up of the body’s own cells, and the immune system takes safety precautions to avoid attacking these cells.

In addition, immune cells often end up attacking the “foreign” virus vehicle more aggressively than the body’s own cargo. With almost all anti-cancer therapies of this type developed so far, therefore, the desired effect on the tumor has not materialized. Finding the appropriate vehicle is just as relevant in terms of efficacy as choosing the tumor component as the point of attack.

Arenaviruses as vehicles

The research group led by Professor Daniel Pinschewer of the University of Basel had already discovered in previous studies that viruses of the arenavirus family are very suitable as vehicles for triggering a strong immune response. The group now reports in the newspaper Cell Reports Medicine that the combination of two different arenaviruses has produced promising results in animal experiments.

The researchers focused on two distant viruses, called Pichindus virus and lymphocytic choriomeningitis virus, which they adapted via molecular biology methods for use as vaccine vectors. When they took the approach of administering the selected tumor component first with one virus and then later with the other, the immune system shifted its attack away from the vehicle and more towards the cargo.

Using two different viruses, one after the other, we focus the triggered immune response on the real target, the tumor molecule. “

Daniel Pinschewer, Professor, University of Basel

Tumor eliminated or slowed down

In experiments on mice, the researchers were able to measure a powerful activation of killer T cells that kill cancer cells. In 20% to 40% of animals – depending on the type of cancer – the tumor disappeared, while in other cases the rate of tumor growth was at least temporarily slowed down.

“We cannot yet say anything about the effectiveness of our approach in humans,” Pinschewer points out. However, ongoing studies with cancer therapy based on a single arenavirus have already shown promising results. It cannot be assumed that the effects on tumors in animal experiments translate directly into the effect on the corresponding cancer types in humans. “However, since therapy with two different viruses works better in mice than therapy with a single virus, our research results make me optimistic,” adds Pinschewer.

The biotechnology company Hookipa Pharma, of which Pinschewer is one of the founders, is currently studying the effectiveness of this new approach to the treatment of cancer in humans. “We are currently exploring what our approach on its own can actually achieve,” says the researcher. “If this is successful, a wide range of combinations with existing therapies could be considered, in which the respective mechanisms join forces to further eliminate tumors.”