New T Cell Therapy Could Transform Glioblastoma Care

Recurrent glioblastoma leaves patients with almost no effective treatments to fall back on. Standard therapies typically combine surgery with chemotherapy, but the disease usually comes back in a harsher, harder-to-treat form. 

Median survival after recurrence is less than a year. A new Phase I trial published August 6 in the journal Nature Medicine suggests an experimental immunotherapy may finally offer these patients another option. 

The treatment relies on CAR-T cell therapy, an approach that re-engineers a patient’s own immune cells to hunt down cancer. Researchers trained the modified cells, known as CAR-T cells, to target B7-H3, a protein found on the surface of most glioblastomas but largely absent from healthy tissue. 

Scientists first linked B7-H3 to cancer in 2001 and have since studied it in tumors of the colon, lungs, and breast, though its exact biological role remains unclear. 

Brain cancers pose a unique obstacle: many promising cancer drugs cannot cross the blood-brain barrier. To get around that, the research team took a different route entirely, threading a catheter directly into the tumor and bypassing the bloodstream altogether. 

The trial enrolled fifteen patients whose glioblastoma had resisted every prior treatment and tested three dose levels in sequence after confirming each tumor expressed B7-H3. Most participants tolerated the experimental treatment relatively well, with only mild reactions like fever, nausea, and skin irritation. 

Three developed more severe complications, among them swelling inside the skull and seizure activity, all of which were brought under control with medical care. Since the roughest reactions showed up mostly at the top dose, the team is now pointing to the middle dose as the preferred dose going forward. 

Early signs of effectiveness stood out even in this small, safety-focused trial. Cancer growth slowed or reversed in just over half the group, and one patient has shown no trace of the disease for three years running. 

One of the study’s co-principal investigators, a Yale Cancer Center immunobiology researcher, said the trial had already produced encouraging clinical results by shrinking tumors in patients who had run out of alternatives. 

Researchers, working with collaborators in Beijing and at the biotech firm Tcelltech, now plan a Phase II trial to test the therapy in a larger patient group. They also intend to refine the CAR-T cells further, aiming to sharpen their cancer-fighting punch and make that effect last longer, with that next-generation version expected to be studied over the coming months. 

With many other entities, such as CNS Pharmaceuticals Inc. (NASDAQ: CNSP), hitting notable milestones in their efforts to bring to market therapeutics targeting brain cancer, it may not be long before cancers of the brain are easily treatable. 

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