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A Vaccine To Prevent Cancer Evolution

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A cancer vaccine could be an effective way to prevent cancer from evolving and becoming resistant to treatment, new research suggests.

Scientists were investigating the use of a cancer-killing virus in clinical trials, and observed, as they had also seen in mice, that although some patients initially responded to the treatment, their tumours soon became resistant.

The researchers showed that the specific mutations causing tumour cells to become resistant to the viral treatment, could be anticipated and exploited using a vaccine which, when tested in mice, was shown to trigger the immune system to destroy treatment resistant tumour cells.

The findings could be applicable to other types of therapy that drive drug resistance, such as targeted drugs like PARP inhibitors.

A vaccine for cancer evolution

The international study – carried out by scientists at The Institute of Cancer Research, London, the Mayo Clinic in Rochester, US, and the University of Leeds – is the first to show that a vaccine of this type can be used to overcome cancer evolution.

The findings are published in Nature Communications, and the study was funded by The National Institutes of Health, The European Research Council, The Richard M. Schulze Family Foundation, Mayo Foundation, Cancer Research UK, Shannon O’Hara Foundation, and Hyundai Hope on Wheels.

Tumour cells treated with an anti-cancer virus are known to mutate and evolve to escape the virus, rendering the viral treatment less effective.

The scientists found that a predictable mutation occurred in the tumour cells in response to infection with the virus.

Vaccine triggered immune system to destroy cancer cells

Virus treatment caused a mutation within the cancer cells, in a gene called CDSE1, which usually protects against viruses by slowing their replication.

The mutated CDSE1 protein, produced by the CDSE1 gene, created a unique antigen – a structure recognised by the immune system as a target – which the researchers used to develop a vaccine.

The researchers produced a vaccine targeting the mutation, and showed that injecting the vaccine into mice that had been treated with the virus triggered the immune system to destroy the drug resistant tumour cells, killing the cancerous cells and therefore reducing the size of their tumours.

'Trap and ambush' approach

They exploited the tumour’s defence mechanism by vaccinating against the mutated cells. This they called a ‘trap and ambush’ approach; forcing a tumour to evolve in a specific way as a defence mechanism against treatment, and ambushing it by vaccinating against this defence mechanism. This vaccine triggers the immune system to destroy the drug resistant tumour cells, preventing the cancer from further evolving.

This work will be developed further by the new Centre for Translational Immunotherapy (CTI) at The Institute of Cancer Research (ICR), a virtual platform bringing together staff and students from the ICR, and The Royal Marsden NHS Foundation Trust aiming to develop a greater understanding of how immunotherapy works.

Study leader Professor Alan Melcher, Professor of Translational Immunotherapy at The Institute of Cancer Research, London, said:

“In this study, we used a ‘trap and ambush’ approach, in which initial treatment with a virus caused tumour cells to mutate in a predictable way, before precisely targeting the mutations with a vaccine, preventing the cancer from progressing further.

“This principle may be more widely applicable, as tumours becoming resistant to drugs is a big problem across multiple types of treatment. We are now exploring the possibility of applying this type of approach to other therapies which drive tumour mutation and evolution.”

Reference: Kottke T, Tonne J, Evgin L, et al. Oncolytic virotherapy induced CSDE1 neo-antigenesis restricts VSV replication but can be targeted by immunotherapy. Nat Commun. 2021;12(1):1930. doi: 10.1038/s41467-021-22115-1

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