Cancer Vaccines Could Be Supercharged With High Levels of APOBEC3B

A new cancer vaccine study found ‘supercharging the mutation rate in cancer cells can create a powerful vaccine that is able to boost the effectiveness of immunotherapy.’

These UK-based scientists forced cancer cells in mice to evolve much more rapidly than usual when using a molecule called APOBEC3B.

They reported on February 7, 2020, that these highly mutated cancer cells could be used to create a vaccine for each individual cancer type, which amplified the effects of immunotherapy.

Led by scientists at The Institute of Cancer Research, London, the Mayo Clinic in Rochester, US, and the University of Leeds, this study is reported to be the first to show that APOBEC3B’s role in driving cancer evolution can be used to create new vaccines, which can boost the immune response.

The researchers first showed they could drive rapid genetic changes in human cancer cells in the lab using high levels of APOBEC3B, which is able to edit the DNA code of cells, giving rise to genetic changes that can be seen as ‘signatures’ or ‘footprints’.

This genetic analysis revealed more than a million extra mutations in the cells expressing APOBEC3B, compared with control cells. 

Of these, around 68,000 contained the classical APOBEC signature. 

These genetic signatures made cancer cells vulnerable to treatment with immune checkpoint blockade, a major strategy in immunotherapy.

However, by generating new genetic changes, APOBEC3B can also drive cancer evolution and help cancer cells become resistant to chemotherapy.

So rather than give APOBEC3B directly to tumors as a treatment, the researchers instead used the genetic signature it left behind to create individual cancer vaccines, each tailored to the particular genetic profile of a specific tumor.

The researchers want to take their new technique for creating personalized vaccines into the clinic as early as next year – starting with a trial in children with brain tumors.

Study author Professor Alan Melcher, Professor of Translational Immunotherapy at The Institute of Cancer Research, London, said in a related press release, “Our new study rather paradoxically takes advantage of a mechanism used by cancers to rapidly evolve and become resistant to chemotherapy, and instead makes them much more vulnerable to the effects of immunotherapy.”

“We have supercharged genetic changes in cancer in order to create cancer vaccines, which are tailored to the genetic code of these tumors, and can boost the immune response against them.”

“By combining our vaccines with checkpoint inhibitor chemotherapy, we’ve shown in mice that it’s possible to cure tumors in a variety of locations, including the brain.”

“Our new approach has the potential to be effective against cancers that do not currently respond to treatment, and we’re keen to take it into clinical trials as soon as possible.”

The Institute of Cancer Research (ICR) has been focusing on increasing its understanding of APOBEC protein molecules, which are crucial to the ability of the immune system to adapt to different infectious diseases – but are also hijacked in many cancers to speed up the evolution of drug resistance.

The ICR – a charity and research institute – is creating a new £75 million Centre for Cancer Drug Discovery to study molecules like APOBEC3B, with the aim of creating new cancer treatments that can overcome the major challenge of cancer evolution and drug resistance.

This study was supported by a variety of funders – the National Institute of Health, the European Research Council, the Richard M. Schulze Family Foundation, the University of Minnesota and Mayo Clinic Partnership, Cancer Research UK, the Shannon O’Hara Foundation, Hyundai Hope On Wheels, and a research grant from Oncolytics Biotech.

No conflicts of interest were disclosed.

Cancer vaccine development news published by Vax-Before-Cancer.