Designer Viruses Stimulate the Immune System to Fight Cancer

Most cancer cells only provoke a limited reaction from the immune system – the body’s defense mechanism – and can thus grow without appreciable resistance. By contrast, viral infections cause the body to release alarm signals, stimulating the immune system to use all available means to fight the invader.

Bolstered defenses

Immunotherapies have been successfully used to treat cancer for many years; they “disinhibit” the body’s defense system and so also strengthen its half-hearted fight against cancer cells. Stimulating the immune system to specifically and wholeheartedly combat cancer cells, however, has remained a distant goal. Researchers lead by Professor Daniel Pinschewer from the University of Basel and Professor Doron Merkler from the University of Geneva have now succeeded in manufacturing innovative designer viruses that could do exactly that.

The researchers built artificial viruses based on lymphocytic choriomeningitis virus (LCMV), which can infect both rodents and humans. Although they were not harmful for mice, they did release the alarm signals typical of viral infections. The virologists also integrated certain proteins into the virus that are otherwise found only in cancer cells. Infection with the designer virus enabled the immune system to recognize these cancer proteins as dangerous.

The unique combination of alarm signals and the cancer cell protein stimulated the immune system to create a powerful army of cytotoxic T-lymphocytes, also known as killer cells, which identified the cancer cells through their protein and successfully destroyed them.

Hope for new cancer treatments

The treatments available to cancer patients have developed enormously in the last few years. However, as the researchers report, current treatments are still inadequate in combating many forms of cancer. “We hope that our new findings and technologies will soon be used in cancer treatments and so help to further increase their success rates,” says the study’s senior author, Professor Daniel Pinschewer.

Original article

Sandra M. Kallert, Stephanie Darbre, Weldy V. Bonilla, Mario Kreutzfeldt, Nicolas Page, Philipp Müller, Matthias Kreuzaler, Min Lu, Stéphanie Favre, Florian Kreppel, Max Löhning, Sanjiv A. Luther, Alfred Zippelius, Doron Merkler, & Daniel D. Pinschewer
Replicating viral vector platform exploits alarmin signals for potent CD8⁺ T cell-mediated tumour immunotherapy
Nature Communications (2017), doi: 10.1038/ncomms15327

Further information

• Professor Daniel Pinschewer, University of Basel, Department of Biomedicine, Tel. +41 61 267 32 70, Email: daniel.pinschewer@unibas.ch
• Professor Doron Merkler, Université de Genève, Département de Pathologie et Immunologie, E-mail: doron.merkler@unige.ch