Scientists and clinicians at Cardiff University have recently completed an exciting clinical trial which used two new treatment strategies to boost the power of the immune system in patients with end-stage bowel cancer. This early phase study is believed to be amongst the first immunotherapy trial in bowel cancer to show a significant improvement in survival outcomes for patients with advanced disease.
Immunotherapy is fast becoming the most promising treatment for cancer, with skin cancers such as melanoma demonstrating great successes by using drugs that activate the immune system to kill cancer cells. However, up until now, very few patients with bowel cancer have benefited from this type of treatment.
The TaCTiCC (TroVax and Cyclophosphamide Treatment in Colorectal Cancer) trial, supported by Cancer Research Wales, was built upon earlier work funded by the charity. Previously, Cardiff based scientists working in the area of immunology, discovered how bowel cancers can disguise themselves in the body by manipulating the normal function and balance of the immune system.
The changes prompted by the tumours lead to an inappropriate rise in the number of cells suppressing the immune system in the blood of patients. In healthy individuals, such mechanisms serve to switch off immune responses after the job of fighting infection is complete, and help protect against the development of allergies and autoimmune diseases.
However, the Cardiff team discovered how cancers are able to hijack this normal process in order to survive. This prevents other types of beneficial immune cells from attacking cancers, allowing the tumour to grow and spread, unchallenged by the body’s natural defenses.
Armed with this knowledge, the team set to reverse this process and boost the anti-cancer fighting properties of the immune system, using a cancer vaccine (called TroVax), in order to train the immune system to better recognise tumours, whilst simultaneously removing the problematic immune suppressor cells.
The latter was achieved using very low doses of a chemotherapy agent called cyclophosphamide, which in small amounts is deleterious to immune suppressor cells, but has no effect on the beneficial and protective immune cells that attack cancer.
In total 55 patients with bowel cancer that had typically spread to the liver and lungs, were recruited to the trial at Velindre Cancer Centre, where they were treated with either a cancer vaccine, and/or low dose chemotherapy to induce an enhanced anti-cancer immune response. Patients whose immune system could be boosted lived on average for 20 months, compared to 10 months in those who failed to respond to the new treatments. Remarkably, patients who mounted the biggest immune responses demonstrated the greatest increase in survival, with good quality of life and few side-effects reported.
Work is ongoing to understand why some patients were not able to respond to treatment; early indications suggest that the immune system in these individuals has become dysfunctional, with high levels of inflammatory markers in their blood. This offers the hope that future trials may be able to utilise other already existing drugs to target these inflammatory molecules and so remove the additional brakes that some tumours seem to place on the patients’ own immune system.
Larger clinical trials are now in the pipeline to verify these findings. In particular, the team aim to test the immunotherapies in patients with earlier stages of bowel cancer, in a bid to prevent or delay patients from relapsing and developing metastases in the first place, following successful initial treatment.
Professor Andrew Godkin, consultant gastroenterologist from Cardiff University, School of Medicine, who designed and led on the trial said, “We are really delighted with the results of this study, at many levels. Firstly, the patients who took part were extremely kind and generous with their time. Most importantly, the study showed that patients who respond by generating immune responses to up-regulated, tumour proteins do well, and this is a fundamentally important finding. The clear benefit to patients opens the door for larger downstream immunotherapy trials which have the potential to expand future treatment options of colon cancer. It also shows that collaborations between scientists, pathologists, clinicians and surgeons, in Cardiff and across Wales can really drive forward exciting new research into cancer, and I am grateful to have such colleagues.
Liz Andrews, Charity Director of Cancer Research Wales said, “As bowel cancer represents the second leading cause of cancer death in Wales, this study represents a big step forward in the management of a disease that is very difficult to treat in the advanced stages. We as a charity are proud to have supported this work as we continue to seek further breakthroughs in this very exciting field of cancer treatment”.