A B.C. research team that helped pioneer Canada’s first homegrown CAR-T cell therapy for cancer is now taking on one of modern medicine’s toughest frontiers: solid tumours.
At the Deeley Research Centre in Victoria, Dr. Julian Smazynski and Nicolette Fonseca are forging new frontiers in immunotherapy, using the body’s own immune system to fight the disease.
CAR-T therapy begins with drawing blood from a patient, isolating their white blood cells in the lab, and then engineering them so they can express a new protein receptor on their surface.
That protein, called a CAR (chimeric antigen receptor), allows a white blood cell to recognize and bind onto a cancer cell, triggering the white blood cell to kill it.
What makes those modified white blood cells particularly effective is that they act a a “living drug,” capable of surviving and functioning within the body.
“They can continuously seek out and destroy cancer cells until the cancer is hopefully eliminated. Some of them may even persist as part of the immune system, providing longer-term protection,” Smazynski said.
Smazynski calls it “one of the most exciting” advances in cancer research over the last two decades, and the Deeley Research Centre has been at the forefront. According to BC Cancer, it was the first in-Canada manufacturing and clinical delivery program for CAR-T.
“In only a few years, we were able to introduce these therapies manufactured in our labs and deliver them to Canadian patients,” Smazynski said. “We’ve since treated nearly 100 people with those early versions of CAR-Ts, and we’re moving at a pace that rivals some of the biggest U.S. labs.”
CAR-T cells aren’t new – they were first invented in the late 1980s by Israeli immunologist Zelig Eshhar, but didn’t reach the clinical mainstream until early versions were FDA approved in 2017. What makes their application in Victoria particularly exciting is the development of novel CAR designs specifically engineered to target solid tumours, including ovarian and pancreatic cancers, which remain among the most challenging malignancies to treat.
Solid tumours are much trickier to destroy than liquid cancers – leukemias and lymphomas – which BC Cancer Deeley Research Centre targeted in their first clinical trial launched in 2019. Think of solid tumours like castles, with more complex blockades and defences rather than solo armed men running around in a field.
Solid tumours also have a host of different markers on the surface, and if CAR-T cells don’t target the right marker, they could end up also attacking other healthy organs or tissues in the body.
That’s where Smazynski’s team’s research at the Deeley Research Centre comes in: the solution is a new CAR-T cell that targets mesothelin – a protein often found in high levels on solid tissue cancers, but conveniently, less common on other healthy tissues.
“These proteins act as a nice flag on the cell surface that says, ‘Hey, I’m a cancer.’ That flag might exist in other parts of the body, but at a level that we can minimize toxicity to,” he said. It offers much more precision compared to the “carpet-bomb approach” of chemotherapy, he said.
Even though they’ve yet to test these mesothelin CAR-T cells in humans, the results in preclinical mouse models are already promising. “We’re seeing completely curative responses,” Smazynski said.
Further boosting his confidence is the remarkable success of BC Cancer’s 2019 CAR-T clinical trial for leukemias and lymphomas, which he says worked “extremely well.” Nearly a hundred patients who had run out of treatment options took part in the study, and an impressive 43 per cent experienced a complete regression of their cancer.
The next step toward proving success in solid tumours is enabling a Phase I clinical trial, expected to launch in 2027, Smazynski said. The trial would likely treat between 12 and 24 patients to confirm the therapy’s safety. If the results look promising, the team would move to a larger Phase II trial, with the ultimate goal of securing Health Canada or FDA approval to make the treatment available to more patients.
Simultaneously, Dr. Nicolette Fonseca is pioneering research to make immunotherapy effective for prostate cancer by developing a blood test that detects tumour mutations and guides personalized immune-based treatments.
The teams are working alongside Dr. Brad Nelson, the Lynda and Murray Farmer immunotherapy chair, who built the DRC’s immunotherapy from the ground up.
“Most of the time these things happen very slowly over decades, but being able to translate my research from the lab bench to the clinic is a rare experience in science and academia,” Smazynski said. “I feel extremely honoured and privileged to be able to do this work alongside the amazing team of colleagues at the DRC.”
He owes that journey to his “beautiful” home in Victoria, a place where he studied at both UVic and Camosun, and then found his calling at the Deeley Research Centre.
“It’s an amazing place for every level of science or student who’s interested in research on any capacity,” he said, noting volunteer opportunities, a high school internship program and undergraduate co-op experiences.
“We’re not only running these clinical trials and doing research, but we’re really educating the next generation of new scientists and creating more opportunities to build in our own community and across Canada.”
That momentum is only building, he said. While the upcoming solid tumours trial is groundbreaking, Smazynski feels as though there is much more to come.
“We’re still in the early days of CAR-T cell therapy, kind of like the first automobiles, which were revolutionary for their time. But with the new ideas we’re testing in the lab, we’re now building the next generation of immunotherapy ‘sport CARs’, poised to be more capable, precise, and ready to take on the toughest challenges, like solid tumours,” he said. “And that’s where we’re really excited.”