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Genetically modified virus may shrink incurable brain cancers

People with incurable melanomas and brain or breast cancers are to receive injections of genetically modified viruses that may shrink their tumours
Tiny phages that usually infect microbes could fight cancer
Science Photo Library/Getty

People with incurable melanomas and brain or breast cancers are to get injections of tumour-fighting viruses.

The trial will test the safety of a virus that has been engineered to shrink tumours – an approach that holds promise for a range of cancers, including deadly brain tumours.

The idea of using viruses to kill cancers goes back more than a century, inspired by anecdotal reports of some people with viral infections being cured of malignancies. But turning viruses that can infect and kill human cells into a safe and effective treatment that targets only tumour cells has proved tricky.

Researchers are making progress at last. In 2015, the US Food and Drug Administration approved the first ever virus-based cancer treatment – a genetically modified herpes virus for advanced melanomas that can’t be completely removed by surgery. Many other virus-based treatments are in development.

Amin Hajitou at Imperial College London and his colleagues have come up with an unusual form of viral treatment, based on a phage – a kind of virus that normally only attacks bacteria.

In principle, it should be safer to use engineered phages in people than viruses that normally infect humans. The phages are designed to bind to cancer cells and inject DNA into them, but these modified phages can’t replicate. This means that they can’t spread to healthy tissue, unlike viruses that normally attack humans.

Hajitou and his team developed this phage by giving it genetic instructions that enable it to bind to a protein often found on the outside of cancer cells, and then inject its DNA into them. They also gave it genes that code for toxic proteins. Once injected with these genes, cancer cells begin to make the proteins, and then die.

In tests in dogs, the phage shrank tumours and, in some cases, made them completely disappear. Hajitou says this phage is now set to begin the first stages of human trials later this year. The trial will take place at the Rutgers Cancer Institute in New Jersey and involve volunteers whose breast, brain or melanoma cancers haven’t responded to other treatments.

Hajitou is already working on a more advanced version of the phage treatment to target glioblastoma, a type of brain cancer with few treatment options. At the moment, around half the people diagnosed with it die within 15 months.

Glioblastoma cells often resist a cancer drug called TMZ by activating genes that block it. Hajitou’s team has taken the code for the genetic switch that fires up these genes, and added it to the engineered phages. This means that, when infected tumour cells try to use these genes to resist the drug, they will make even more of the toxic proteins.

Seek and destroy

When mice with human glioblastomas were given this phage and TMZ together, they survived for two months, whereas controls died after a month. The treated mice also lived longer than those given either the phage or TMZ on its own. Human trials are still several years away, says Hajitou.

The phage is promising for brain cancers in particular because, after being injected into the bloodstream, it seeks out tumours around the body and can cross the blood-brain barrier. By contrast, most other experimental viral cancer treatments have to be injected directly into tumours.

It would be much easier to roll out treatments that can be delivered by routine injections, says Alan Melcher at the Institute of Cancer Research in London.

This designer phage also doesn’t need to carry the genes for replicating itself, so more DNA can be engineered into it, up to 20,000 letters of code. This means there is scope for adding extra genes to enhance its effectiveness, while further DNA edits could enable the phage to target other types of tumours.

EMBO Molecular Medicine

Topics: Cancer / Genetic modification / Viruses