Associate Professor Niall Tebbutt, Principal Investigator of the MODULATE trial

MODULATE: A new approach to immunotherapy for colorectal cancer patients

Colorectal cancer, or bowel cancer, is the most commonly diagnosed cancer in Australia. If it is diagnosed early, there can be effective treatments, but patients with advanced colorectal cancer that has spread to other organs cannot currently be cured.

One promising treatment method for some forms of cancer is immunotherapy, which uses the body’s own immune system to target and attack cancers. Immunotherapy works by stimulating lymphocytes, a type of white blood cell, which have infiltrated tumours.

“One of the more promising treatments in oncology in general at the moment is immunotherapy,” says Associate Professor Niall Tebbutt, Principal Investigator of the MODULATE trial. “That plays a role in lots of other cancers, but generally bowel cancer is resistant.”

In bowel cancer, immunotherapy treatment is ineffective for over 95% of patients, because lymphocytes are unable to enter bowel cancer tumours at all.


How MODULATE works

The MODULATE trial aims to test whether it is possible to enable lymphocytes to enter bowel cancer tumours, and to attack them once they are inside. Researchers will recruit 90 patients at 15 sites across Australia. Everyone who joins the trial will have advanced bowel cancer, and will have exhausted all standard treatments. This trial provides them with the option of trying an experimental treatment which may prove to have an effect.

Patients will be split into two groups to test two approaches. The first group will receive an inhibitor of the signalling protein STAT3 – STAT3 can enable tumours to evade the immune system. The second will receive a vascular disrupting agent, which will damage the blood vessels of a tumour to encourage lymphocytes to enter.

Both of these approaches are experimental as they have not been tested on people with bowel cancer before. Researchers hope that one of the approaches will be effective in shrinking tumours.

Associate Professor Tebbutt notes that since this trial is experimental, “If we could learn something that could enable us to design a better study down the track, it would be worthwhile.” If the trial reveals an effective strategy for stimulating lymphocytes to enter tumours, it will be step towards developing effective immunotherapy for bowel cancer.