‘Seek and destroy’: unlocking the power of the immune system with radiotherapy
Grant information
Institution – University of Oxford
Researchers – Professor Katherine Vallis
Grant award - £278,022
Duration of funding – 2020-2024
Status - Complete
Reference – MA-IMM19-009
We’ve demonstrated that 177Lu-PSMA stimulates the immune system, and by analysing gene activity changes after treatment, we’re identifying the most effective drug combinations to amplify its anti-cancer effects.
Why did we fund this project?
Prostate-specific membrane antigen (PSMA) is a protein found in large amounts on the surface of prostate cancer cells.
177Lu-PSMA is a radioactive drug that travels through the blood stream and binds to PSMA, delivering radiation directly to prostate cancer cells without damaging the surrounding healthy cells.
Professor Kate Vallis and her team aimed to investigate whether this ‘seek and destroy’ radiotherapy also stimulates the body’s natural defence mechanism - the immune system.
What did the team do?
The team investigated whether 177Lu-PSMA triggers immunogenic cell death, a process that activates the immune system to recognise and destroy cancer cells.
They then investigated how 177Lu-PSMA affects different immune cells and identified key proteins involved in their response to treatment.
Using these insights, the researchers developed drugs that target these proteins, with the aim of enhancing the immune response following 177Lu-PSMA treatment.
What did the team achieve?
Excitingly, the team demonstrated that 177Lu-PSMA does trigger immunogenic cell death and increases the number of immune cells activated to target prostate cancer cells.
However, they also found that 177Lu-PSMA reduces the ability of a specific type of immune cell, called a macrophage, to destroy cancer cells.
To try to counter this effect, the team successfully developed drugs that block a key protein involved in reducing macrophage activity and hope they may help these cells remain active during treatment.
What does this mean for men?
Combining 177Lu-PSMA with drugs that boost the immune response could make the treatment more effective and help men with prostate cancer live longer and better lives.
The researchers now plan to test these drugs alongside 177Lu-PSMA in mice, and we look forward to sharing updates as this promising research progresses.
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