Canadian Researchers Develop Next-Generation CAR-T Therapy Targeting Solid Tumors with Mesothelin
核心洞察
Victoria's Deeley Research Centre has developed novel CAR-T cells targeting mesothelin protein to treat solid tumors including ovarian and pancreatic cancers.
The team achieved complete curative responses in preclinical mouse models and plans to launch Phase I clinical trials in 2027.
Building on their success with liquid cancers where 43% of patients experienced complete regression, researchers are advancing toward one of immunotherapy's most challenging frontiers.
Researchers at Victoria's Deeley Research Centre are advancing CAR-T cell therapy into one of modern medicine's most challenging territories: solid tumors. The team, led by Dr. Julian Smazynski and Nicolette Fonseca, has developed next-generation CAR-T cells specifically engineered to target mesothelin, a protein highly expressed on solid tissue cancers but less common on healthy tissues.
Breakthrough in Solid Tumor Targeting
The Victoria team's approach represents a significant advancement over existing CAR-T therapies, which have primarily succeeded against liquid cancers like leukemias and lymphomas. Solid tumors present unique challenges, functioning "like castles, with more complex blockades and defences rather than solo armed men running around in a field," according to Smazynski.
The key innovation lies in targeting mesothelin, which acts as a distinctive marker on cancer cells. "These proteins act as a nice flag on the cell surface that says, 'Hey, I'm a cancer,'" Smazynski explained. "That flag might exist in other parts of the body, but at a level that we can minimize toxicity to."
Promising Preclinical Results
Despite not yet testing these mesothelin CAR-T cells in humans, the preclinical data demonstrates exceptional promise. "We're seeing completely curative responses" in mouse models, Smazynski reported. This success builds on the team's established track record with liquid cancers, where their 2019 clinical trial achieved remarkable results.
In that earlier study, nearly 100 patients who had exhausted other treatment options participated, with 43% experiencing complete cancer regression. "It worked extremely well," Smazynski noted, providing confidence for the solid tumor application.
Clinical Development Timeline
The team plans to launch a Phase I clinical trial in 2027, treating between 12 and 24 patients to establish safety parameters. Success in this initial phase would lead to larger Phase II trials, with the ultimate goal of securing Health Canada or FDA approval.
According to BC Cancer (搜索), the Deeley Research Centre operated Canada's first in-house CAR-T manufacturing and clinical delivery program. "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."
Expanding Immunotherapy Applications
Parallel research efforts include Dr. Nicolette Fonseca's work developing blood tests that detect tumor mutations to guide personalized immune-based treatments for prostate cancer. The team collaborates with Dr. Brad Nelson, who holds the Lynda and Murray Farmer immunotherapy chair and built the center's immunotherapy program from inception.
Technology Advantages
CAR-T therapy involves extracting a patient's white blood cells, engineering them to express chimeric antigen receptors (CARs) on their surface, then reinfusing them. These modified cells function as "living drugs" that can continuously seek and destroy cancer cells while potentially providing long-term immune protection.
The approach offers significant precision advantages over conventional treatments. As Smazynski described, it provides much more targeted therapy compared to the "carpet-bomb approach" of chemotherapy.
Future Prospects
Smazynski characterizes the current state of CAR-T therapy as analogous to early automobiles - revolutionary but with substantial room for advancement. "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.
The research represents a rare example of rapid bench-to-bedside translation in academic medicine. "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 noted.