Cancer treatment has advanced dramatically in recent years, particularly with the rise of immunotherapy. These treatments harness the body’s immune system to find and destroy cancer cells. For some patients, they have been life changing. But for many others, they simply don’t work.
One reason is that certain tumours are “cold” and can hide from the immune system and cancer therapies, continuing to grow undetected. At the same time, many existing treatments act like wrecking balls, destroying healthy cells along with cancer cells and causing significant side-effects for patients.
Dr. Bowen Li, GSK Chair in Pharmaceutics and Drug Delivery at the Leslie Dan Faculty of Pharmacy, University of Toronto, and Canada Research Chair in RNA Vaccines and Therapeutics, is working to address both challenges at once. With $525,000 from a Terry Fox New Investigator Award, his team is developing a programmable mRNA therapy designed to detect cancer cells and trigger their destruction while leaving healthy tissue untouched.
“We want to overcome the all-or-nothing challenge of immunotherapy to create a system that can not only deliver the drug, but also sense the environment inside the cell before deciding to act,” says Dr. Li, who is also an affiliate scientist at Princess Margaret Cancer Centre, University Health Network.
He uses the analogy of a city skyline. Most buildings represent normal, healthy cells, but hidden among them are cancerous ones that look almost identical from the outside. His approach will give construction workers a sort of scanner that, when close enough, senses hazardous buildings and flags them for destruction.
To achieve this precision in the body, they will package a set of smart instructions in messenger RNA (mRNA) and deliver them using tiny lipid nanoparticles. Once inside cells, the mRNA, which includes a programmable molecular “sensor,” will detect unique genetic or protein signatures (“barcodes”) distinguishing cancer cells from healthy ones. When the sensor detects that barcode, it switches on.
Once activated, the mRNA instructs the cancer cell to produce a protein that triggers a specific type of cell death, killing that cell and creating a ripple effect among other cancer cells.
“Rather than delivering the therapy to every single cancer cell, targeting even five or ten percent can activate an immune response that clears the remaining tumour,” says Dr. Li.
The project will initially focus on lung cancer, the leading cause of cancer-related death worldwide. Lung tumours are often diagnosed at advanced stages, and many patients do not respond to existing immunotherapies. The team will design and test their programmable mRNA system in lung cancer models to demonstrate that it can safely eliminate tumours while stimulating a strong immune response.
If successful, they aim to adapt this platform for other cancers and cold tumours, ensuring it can be accessed by patients across the country.
“The ultimate goal of our project is to make sure every patient gets a blueprint perfectly designed for their unique type of cancer and can benefit from immunotherapy,” says Dr. Li.
“Together, we are helping finish Terry Fox’s marathon against cancer by ensuring that no tumour is too cold to be treated, and no treatment is too toxic to be safe.”