Researchers at McMaster University have developed a new immunotherapy strategy that simultaneously attacks glioblastoma tumors and the immune cells that help them grow. By using Chimeric Antigen Receptor T-cell (CAR-T) therapy to target the GPNMB protein, the study—published July 1 in Nature—demonstrated the ability to eliminate detectable tumors and achieve long-term disease-free survival in pre-clinical models.
Why is glioblastoma so difficult to treat?
Glioblastoma is one of the most aggressive and difficult-to-treat forms of cancer. While traditional treatments often focus on the tumor mass itself, the cancer often survives by manipulating its surroundings.
According to the study, glioblastoma hijacks macrophages—immune cells that normally defend the body against infection—to help the tumor grow and resist treatment. These hijacked cells help suppress immune attacks and create a protective environment for the cancer.
“Instead of treating the tumor as only a mass of cancer cells, we suggest that we must treat glioblastoma as a connected tumor-immune ecosystem,” says senior author Sheila Singh, a professor of surgery at McMaster.
“Our approach attacks both the tumor and the environment that allows it to thrive. We’re going beyond targeting the cancer alone and eliminating the immune cells that help shield it from treatment.”
Macrophages are typically part of your body’s defense system, but glioblastoma can “reprogram” them to act as support staff for the tumor instead of attacking it.
How does the GPNMB target work?
The research team identified Glycoprotein non‑metastatic melanoma protein B (GPNMB) as a critical target. This protein is found on both the cancer cells and the tumor-supporting macrophages.
By utilizing CAR-T therapy, the researchers designed cells that recognize GPNMB. This allows the therapy to strike two targets at once: the tumor cells and the immune environment sustaining them. This dual-action approach aims to dismantle the “immune support system” that typically allows brain tumors to survive.
Shan Grewal, a co-lead author and MD/PhD candidate at McMaster, noted that while CAR-T therapy has seen success in treating certain blood cancers, applying it to brain tumors has historically been difficult. Grewal suggests that success in brain cancer may require this specific method of dismantling immune support.
What results were seen in pre-clinical models?
In several pre-clinical models, including those grown from human patient tumors, the therapy successfully eliminated detectable tumors. These models also showed evidence of long-term disease-free survival.
These findings build on existing research regarding GPNMB. For instance, researchers at the University of Calgary recently led a first-in-human clinical trial for patients with metastatic sarcoma—a cancer of the connective tissues—targeting the same protein. Details of that trial were published in Nature Cancer.
The combined findings from both the McMaster and Calgary studies suggest that GPNMB is a promising target across various cancer types, providing a foundation for future clinical applications.
Research Collaborators and Support
The study involved a wide network of international collaborators, including King’s College London, Northwestern University, the University of Calgary, the University of Toronto, and The Hospital for Sick Children.
Funding for this research was provided by the Terry Fox Research Institute, Brain Canada, the Cancer Research Society, Brain Cancer Canada, and the Brain tumor Foundation of Canada.
