Turning the immune system on cancer

Tumours are intrinsically stubborn things, capable of resisting invasion by the body’s natural immune defences, which prevents them from being eradicated.

Now a team of researchers from the Western Australian Institute for Medical Research (WAIMR) have developed a targeted version of a naturally-occurring protein that can penetrate the barriers erected by some tumours, thus allowing immune cells to kill or disable the cancerous cells.

The Perth-based team was led by Professor Ruth Ganss and produced a targeted version of TNF-Alpha, a tumour necrosis factor that is involved in inflammation and precipitating cell death.

These targeted TNF-Alpha cells were directed to a pancreatic tumour, where they made the blood vessels in the tumour more permeable to immune cells, which were then able to enter and attack the tumour.

This raises the prospect of a new treatment that lowers cancer’s defences against the body’s own immune system, thus enabling immunotherapies to become significantly more effect against cancer.

“Until now, immunotherapy has not been very successful in treating cancer because tumours are very resistant to immune cells,” said Dr Anna Johansson, from The University of Western Australia, which is affiliated with WAIMR.

“As a cancerous tumour grows, it forms a solid ball which is difficult for immune cells to get into and even if they can penetrate the tumour, the environment inside it either kills the cells or makes it difficult for them to function.

“We engineered a protein called TNF-Alpha so that it went straight to a pancreatic tumour and stayed there without toxic side effects outside the tumour.

“TNF-Alpha affected the blood vessels in the tumour in a surprising way which opened the solid ball so that immune cells could get inside.

“We thought it might damage the blood vessels because TNF-Alpha can be very toxic, but in low doses it actually improved them and increased healthy blood flow, helping immune cells to get inside the cancer.”

The discovery sheds light on the role that low dose TNF-Alpha plays in enhancing the ability for chemotherapy drugs to work, and could open new avenues for cancer treatment.

The study was published last week in the Proceedings of the National Academy of Sciences.