CAR-T cell therapy shows potential to eliminate aggressive glioblastoma
· News-MedicalA study led by a researcher based at King's College London and McMaster University in Canada reveals how CAR-T cell therapy, a treatment that engineers a patient's own immune cells to recognize and attack cancer, could be used to treat glioblastoma. Glioblastoma is one of the most aggressive and difficult-to-treat cancers, with devastatingly poor survival
In several preclinical models of glioblastoma, including those grown from human patient tumors, the therapy eliminated detectable tumors and led to long-term disease-free survival.
Glioblastoma is extremely hard to treat for many reasons. It aggressively spreads though the brain, forming threads into brain tissue rather than a clear lump which can be removed during surgeries. Even after surgery, microscopic remnants of cancer can remain. The cancer is also made up of multiple different types of cells, making it hard to target with chemotherapy and radiotherapy.
CAR-T therapy has transformed outcomes for some blood cancers, but it has not yet produced the same breakthrough for glioblastoma. Scientists are now investigating how the treatment could be used in glioblastoma, drawing on its known connections with the immune system.
The researchers identified a protein called GPNMB on both glioblastoma cells and tumor-supporting macrophages. This gave the team a rare opportunity to design a therapy that targets the tumor and the immune environment that helps sustain it. By engineering CAR-T cells to recognize GPNMB, the team developed a strategy designed to attack glioblastoma on two fronts at once.
Professor Singh added: "Instead of treating glioblastoma as only a mass of cancer cells, we need to think of it as a connected tumor-immune ecosystem. Our approach targets both the tumor and the environment that allows it to thrive. By going beyond the cancer cells alone, we are also targeting immune cells that help shield the tumor from treatment."
Co-lead author Shan Grewal, an MD/PhD candidate at McMaster, added: "CAR-T therapy has been effective in some blood cancers, but translating that success to brain tumors has been difficult," says "Most approaches have focused on killing cancer cells alone. Our work suggests we may also need to dismantle the immune support system that helps glioblastoma survive."
The researchers stress that more work is needed before the treatment can move toward clinical trials. However, the study introduces a new treatment paradigm for one of the deadliest cancers in oncology by targeting the tumor and its immune defenses at the same time.
Professor Sheila Singh's joint position at King's College London and McMaster University is bringing together scientists at the forefront of research into brain cancer. Within King's, Professor Singh is Head of the Comprehensive Cancer Centre, based at a specialist Innovation Hub.
Scientists from across disciplines at King's work within the Innovation Hub to embed cutting-edge cancer research and access to clinical trials directly into patient care. Last month, His Majesty The King met Professor Sheila Singh and other cancer researchers based at the hub, located at Guy's and St Thomas' NHS Foundation Trust.
Professor Singh added: "Only through collaboration with scientists across the world and with clinicians can we tackle this devastating disease. I've seen firsthand through my work as a neurosurgeon the impact glioblastoma has on patients and their family members and I am committed to developing new treatments to improve outcomes for those affected by brain cancer."
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