Researchers develop personalized immunotherapy against one of the most aggressive brain tumors

Glioblastoma is one of the most aggressive and difficult to treat brain tumors, with low survival rates and limited treatment options. Chemotherapy and radiotherapy bring modest benefits, and relapse is almost inevitable. In this context, the team from the Carlo Besta Neurological Institute in Milan has presented a new strategy based on harnessing the body's immune defenses. The study, published in the journal Nature Communications, marks a possible paradigm shift in the treatment of brain tumors.

• How the new therapy works

The researchers, led by Serena Pellegatta, exploited the potential of T-infiltrating lymphocytes (tr-TILs) - immune cells capable of recognizing and attacking the tumor, but which, in the case of glioblastoma, are present in small numbers and are often "exhausted".

The method involves: harvesting tumor tissue during surgery, isolating reactive T lymphocytes identified by the CD137 marker, multiplying them in the laboratory, preserving immune memory, and reintroducing them into the body to attack cancer cells.

An additional step is blocking the PD-L1 protein, which the tumor uses to hide from the immune system. By inhibiting it, the reprogrammed lymphocytes become even more effective.

• Results obtained so far

The study involved 161 patients with diffuse glioma. The extracted tr-TIL cells were tested in animal models. The results showed a slowdown in tumor growth in 70% of the animals, with a significant increase in survival. The protocol already complies with international Good Manufacturing Practice (GMP) standards, which makes it eligible for clinical application. The next step is to start the ReacTIL clinical trial, which will test the safety and effectiveness of the therapy in human patients.

• A personalized and innovative approach

"Therapy with tr-TIL has the potential to become a concrete option for patients with glioblastoma," said Serena Pellegatta, highlighting the advantage of the immunological strategy, which capitalizes on the body's own resources. In turn, Francesco Di Meco, co-author of the study, emphasized that this therapy could offer real hope for the first time to patients affected by an extremely difficult-to-treat tumor: "The concept has worked against other types of cancer, but it has not been effective so far in glioblastoma. Our study paves the way for immediate clinical application."

• Prospects

If clinical trials confirm the promising results obtained in the laboratory, patients will have access to a personalized and less invasive strategy, capable of offering a real chance of prolonging life and, perhaps, of curing it. For the first time, in the fight against one of the most formidable forms of brain cancer, the patient's immune system becomes the main weapon.