A new weapon against glioblastoma, one of the most aggressive and difficult-to-treat brain tumours, has been developed by a team from the Neurological Institute of Milan.
Their study, published in Nature Communications, harnesses the immune defences of patients to fight the disease.
The research team, led by Serena Pellegatta, focused on tumour-infiltrating T lymphocytes. These immune cells are present in glioblastoma but are typically scarce and often “exhausted”, making them poorly functional.
The method developed by the team isolates and expands in the laboratory functional and reactive tumour-infiltrating T lymphocytes (tr-TIL), tailored specifically to each patient, while preserving their immune memory. Once reinfused, these lymphocytes are potentially capable of recognising and eliminating tumour cells.
Researchers also discovered a mechanism to unmask the tumour. By blocking the PD-L1 protein, which glioblastoma uses to “hide” from the immune system, tr-TILs become even more effective in destroying cancer cells.
The new protocol at Besta begins with material removed during surgery. Neurosurgeons collect the tumour tissue, including immune cells, with a specialised instrument called the ultrasonic dissector. In the laboratory, “reactive” T lymphocytes are isolated using the CD137 marker and cultured with factors that promote their expansion while preserving their immune memory and functionality.
The study involved 161 patients diagnosed with diffuse glioma. In laboratory tests, tr-TILs successfully expanded from patients’ tumours were administered to animal models. Results showed tumour growth slowed in 70 per cent of cases, with a corresponding increase in survival.
The protocol has already been adapted to Good Manufacturing Practices (GMP) standards, a requirement for clinical application. The next step will be the ReacTIL clinical trial, which will test the safety and efficacy of this therapy in glioblastoma patients.
If results are confirmed, patients may gain access to a new personalised strategy for treating glioblastoma. As Besta emphasised, this would address “one of the most difficult challenges in oncology”.
“Our study demonstrates that tr-TIL therapy has the potential to become a concrete option for patients with glioblastoma,” said Pellegatta, director of the Department of Neurosurgery at Besta Hospital and of the School of Specialisation in Neurosurgery at the University of Milan.
“Immune-based tumour treatment strategies are extremely promising because they exploit the body’s own resources, which are otherwise neutralised by the disease. This concept has proven effective against some systemic tumours.”
Francesco Di Meco, Director of the Department of Neurosurgery at Besta Hospital and of the School of Specialisation in Neurosurgery at the Statale University, added: “So far, immune-based treatments have not shown efficacy against glioblastoma, a tumour we have been unable to effectively combat. The study led by Dr. Pellegatta, published in Nature Communications, identifies an effective strategy for targeting glioblastoma cells and lays the foundation for immediate clinical application, offering our patients real prospects for treatment.”