Researchers at McMaster University have developed a new cancer immunotherapy strategy that can simultaneously attack deadly brain tumours and the immune cells that help them grow.
The study, published on July 1, in Nature, focuses on glioblastoma – one of the most aggressive and difficult-to-treat cancers – and immune cells called macrophages that normally help defend the body against infection. Glioblastoma, however, can hijack these cells and use them to help the tumour grow, suppress immune attacks, and resist treatment.
Researchers identified Glycoprotein non‑metastatic melanoma protein B (GPNMB) found on cancer cells and these tumour-supporting macrophages. This presented a unique opportunity to design a therapy that targets both the tumour and the immune environment that helps sustain it. Through the use of Chimeric Antigen Receptor T-cell therapy (CAR-T), the team showed how CAR-T cells can recognize GPNMB and attack the tumour on both fronts at once.
"Instead of treating the tumour as only a mass of cancer cells, we suggest that we must treat glioblastoma as a connected tumour-immune ecosystem," says senior author Sheila Singh, a professor of surgery at McMaster. "Our approach attacks both the tumour 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."
In several pre-clinical models of glioblastoma, including those grown from human patient tumours, the therapy eliminated detectable tumours and led to long-term disease-free survival in those models.
The study builds on earlier work developing CAR-T therapies that target GPNMB, including a first in human clinical trial for patients with metastatic sarcoma – a type of cancer that starts in connective tissues – led by researchers at the University of Calgary. Details of that trial were simultaneously published in Nature Cancer. Together, the studies highlight GPNMB as a promising target across cancer types and provide a foundation for translating this strategy to patients.
"CAR‑T therapy has been effective in some blood cancers but translating that success to brain tumours has been difficult," says co-lead author Shan Grewal, an MD/PhD candidate at McMaster. "Most approaches have focused on killing cancer cells alone. Our work suggests we may also need to dismantle the immune support system that helps the tumour survive."
The researchers stress that more work is needed before the treatment can move toward clinical trials. Collaborators from King's College London, Northwestern University, the University of Calgary, the University of Toronto and The Hospital for Sick Children were involved in the research.
This research was supported by the Terry Fox Research Institute, Brain Canada and the Cancer Research Society, Brain Cancer Canada, and the Brain Tumour Foundation of Canada.
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