New therapy can cure breast cancer in mice

OTTAWA • A new Ottawa research study shows that “triple negative” breast cancer — a particularly aggressive form of the disease — can be successfully treated in mice with a combination of immunotherapies that weaponize the immune system in different ways.

The study was published Wednesday in Science Translational Medicine, a journal devoted to research that advances the prevention, diagnosis and treatment of disease.

It found that the immunotherapies were much more powerful when used in combination than alone.

Researchers at The Ottawa Hospital found that staged immunotherapies (an oncolytic virus before surgery followed by a checkpoint inhibitor after it) cured 60 to 90 per cent of mice with triple negative breast cancer, currently treated with limited success using surgery, radiation and chemotherapy.

Used alone, neither the checkpoint inhibitor nor the Maraba virus had a significant impact on overall survival rates with surgery.

The study’s lead author was Dr. Marie-Claude Bourgeois-Daigneault, a post-doctoral fellow in Dr. John Bell’s research lab.

“It was absolutely amazing to see that we could cure cancer in most of our mice — even in models that are normally resistant to immunotherapy,” BourgeoisDaigneault said.

Bell, a University of Ottawa professor and senior research scientist at The Ottawa Hospital, said the study offers more evidence that the full benefit of immunotherapy will only be realized when the cancer treatments are used in combination.

Oncolytic viruses such as the Maraba can invade a tumour and attack it while also triggering a broad immune response against specific kinds of cancer cells. Meanwhile, checkpoint inhibitors such as Yervoy and Opdivo close a communication pathway that tumours use to “mislead” the immune system and shut down the work of cancer-fighting T-cells.

“They both bring something to the table,” Bell explained. “The viruses, they initiate the immune response and then the immune checkpoint licenses the immune system, engages it, and allows it to be active. We doubled down on immune stimulation, and when we did that, we found it was very effective in preventing (cancer) relapses.”

Bell, one of the country’s leading immunotherapy researchers, is now hoping to establish a clinical trial to test the combination therapy in patients with triple negative breast cancer.

The challenge, Bell said, is to attract funding for that trial in an immunotherapy field now crowded with researchers trying to unlock combinations that will boost the body’s immune response to a tumour. Since checkpoint inhibitors work well for only a minority of cancer patients, there’s a scientific race underway to find an immunotherapy cocktail that can help more people.

“The real problem is that everyone is just throwing stuff against the wall to see what sticks,” Bell said. “What we’re saying is, ‘Let’s stop doing that.’ Why not, instead, have a rational approach and say, ‘This actually makes biological sense so let’s combine these things this way.’

“That’s part of what this study was designed to do: To try to find an indication that makes sense and has potential clinical applicability.”

The mouse study was designed to simulate the typical course of a woman’s breast cancer treatment, and to use the “window of opportunity” that exists between a patient’s diagnosis and surgery. The study found that the most effective course of treatment involved three stages: The administration of an oncolytic virus, then surgery, followed by an immune checkpoint inhibitor.

Viruses are highly evolved infectious agents that can infect, colonize and destroy human cells. Scientists have discovered they’re ideally suited to attacking malignant tumours, which have genetic mutations that make them more susceptible to viral attack.

Oncolytic viruses have the added advantages of triggering a broad immune response against tumours and training that system to identify and attack those cells if they return.