‘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 cancer cells without damaging the surrounding healthy cells.
- Professor Vallis and her team aimed to investigate whether this ‘seek and destroy’ radiotherapy could stimulate the body’s natural defence mechanism - the immune system - to recognise and kill any remaining cancer cells.
What did the team do?
- The team investigated whether 177Lu-PSMA kills cancer cells through a process called immunogenic cell death, which activates the immune system to target cancer cells.
- Gene activity changes following 177Lu-PSMA treatment were analysed to identify key proteins involved in the immune response.
- Drugs that target these key proteins were given to mice in combination with 177Lu-PSMA to see if its anticancer effects could be enhanced.
What did the team achieve?
- Excitingly, the team demonstrated that 177Lu-PSMA does trigger immunogenic cell death and stimulates an overall increase in the number of immune cells activated to target cancer cells.
- Following treatment with 177Lu-PSMA, increased levels of several immune system proteins were detected, including proteins associated with resistance to radiotherapy and others known to activate and recruit anticancer immune cells.
- The team now plan to develop drugs that alter the activity of these key proteins to enhance the effectiveness of 177-Lu-PSMA.
What does this mean for men?
- 177Lu-PSMA is a powerful drug that specifically targets prostate cancer cells, while minimising damage to healthy cells, reducing the side effects of radiotherapy.
- A greater understanding of changes in the immune system following 177Lu-PSMA treatment may help in the development of new drugs that can be used in combination with 177Lu-PSMA.
- Combining this form of radiotherapy with drugs designed to enhance the immune response could improve outcomes for men with prostate cancer.
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