The immune system protects us from infections. It ensures that bugs such as coughs, colds and the flu are normally eliminated without making us seriously ill. It is now known that the immune system can also protect us against cancer.
Cells of the immune system patrol our tissues and eliminate “rogue cells” that might lead to cancer. However, cancer cells have their own tricks and adapt themselves to evade immunity. Cancers hide from immune cells, or switch them off and therefore continue to grow. By the time a cancer is detected by a doctor, it has already escaped the attention of the immune system.
What were the aims of this research project?
The goal of our research was to find new ways to switch immune cells on so that they are able to detect and destroy cancer cells.
Viruses are good at switching the immune system on and some viruses can infect and kill cancer cells. Using viruses that don’t cause harm to patients can help to attack the cancer in two ways:
- The virus can kill the cancer cells directly
- The virus switches on the immune system to attack the cancer cells
Professor Graham Cook, Dr Errington-Mais and Dr Tyler Barr, at the University of Leeds, were interested in how these viruses, known as oncolytic (“cancer-bursting”) viruses switch on a type of immune cell in the blood, called a natural killer cell.
Researchers previously demonstrated in lab studies, and in clinical trials, that the oncolytic viruses switch the killer cells on. With BCRT funding, the University of Leeds team set out to try these viruses to see if they can help to kill Ewing sarcoma cancers.
They had a number of these viruses that have been made at clinical grade, this means they are manufactured specifically for trying in cancer patients. They planned to test these viruses in the lab to see if they killed the Ewing sarcoma cells directly and if they switched on the killer cells to destroy the cancer.
In previous research, the team identified molecules that the Ewing sarcoma cells use, to switch the killer cells off; there are also therapeutic drugs available that block these molecules. As part of this BCRT funded research, they next set out to investigate whether combinations of viruses, this new drug and killer cells together were an effective route to kill Ewing sarcoma.
What were the results of this research project?
The research team successfully demonstrated that oncolytic viruses were indeed able to kill Ewing sarcoma cells grown in the lab (‘cell lines’), both directly and also by activating natural killer cells.
The team also evidenced the efficacy of oncolytic viruses against Ewing sarcoma cells using more complex models, which more closely resemble the disease in patients. However, crucially, the results in these patient-derived Ewing sarcoma cell cultures and 3D tumour models differed significantly from what was observed in cell lines established and cultured in the lab over many years.
The ability of Ewing sarcoma cells to effectively switch off natural killer cells, inhibiting the immune system’s ability to detect and halt the development and progression of cancer, was also evidenced.
These important findings have directly led to a further research project, which will continue the investigation of oncolytic viruses against patient-derived Ewing sarcoma cells specifically.
How could the results of this project improve treatment options for Ewing sarcoma patients?
This research has taken important steps in furthering our understanding of the use of oncolytic viruses in Ewing sarcoma and important underlying interactions with the body’s immune system. The value of these findings is demonstrated in the further funding obtained to progress this research even further, in the hopes of ultimately leading to a much-needed new and targeted treatment for patients with Ewing sarcoma.
The viruses and drugs used in this laboratory-based project are already in clinical trials for other cancers, showing promising results. This therefore means there is the potential for a much faster translation from laboratory to clinic.
This project was also supported by the Ewing Sarcoma Research Trust.
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