A wearable device that beams electric fields into the brain may unlock the full potential of immunotherapy in treating glioblastoma — the deadliest form of brain cancer.
Key Points at a Glance
- Electric fields (TTFields) combined with immunotherapy and chemo extended survival in glioblastoma patients by ~70%
- Inoperable tumors showed even greater response, extending life by 13+ months
- TTFields disrupt tumor growth and recruit immune cells directly into the brain
- This approach may finally make immunotherapy effective against glioblastoma
Glioblastoma has long resisted modern medicine’s most promising weapons. While immunotherapy has transformed outcomes for many cancer patients, glioblastoma — shielded by the brain’s blood-brain barrier — remains notoriously immune to the immune system. But a new clinical study led by Keck Medicine of USC hints at a surprising breakthrough: electricity.
The trial combined three strategies: Tumor Treating Fields (TTFields), which are alternating electric fields delivered through electrodes on the scalp; the chemotherapy drug temozolomide; and the immunotherapy pembrolizumab, a checkpoint inhibitor. Together, this trio extended patient survival by an average of 70% over historical results from chemo plus TTFields alone. Notably, patients with large, inoperable tumors — often the hardest cases — lived 13 months longer on average than those in previous trials.
TTFields work by interfering with the division of cancer cells, pushing and pulling at cellular structures during mitosis. This “scrambling” effect weakens the tumor’s defenses. But researchers also discovered an immunological side effect: TTFields lured more T cells — the body’s immune assassins — into the tumor microenvironment. Once there, these T cells remained active longer and multiplied after pembrolizumab was introduced, creating a robust immune assault on the tumor.
“Think of TTFields as weakening the tumor’s defense line,” said Dr. David Tran, lead investigator and chief of neuro-oncology at Keck Medicine. “When immunotherapy arrives, the immune system can launch a stronger, more focused attack.”
What makes this approach particularly groundbreaking is its effectiveness in glioblastoma’s most resistant scenarios. Large tumors that can’t be surgically removed often correlate with worse outcomes. Yet here, the larger the tumor, the stronger the immune response — possibly because more cancerous tissue gives TTFields and immune cells more targets to rally against.
The study, part of the 2-THE-TOP Phase 2 trial, included 31 newly diagnosed patients. Those receiving the triple therapy survived up to 24–25 months on average, a significant jump from the typical 14–15 months with just chemo and TTFields. A follow-up Phase 3 trial is now underway at 28 centers across the US, Europe, and Israel, and aims to validate these results in over 740 patients by 2029.
For glioblastoma patients, especially those facing inoperable diagnoses, these findings offer a rare dose of hope. By re-engineering the battlefield inside the brain using electric fields, doctors may finally unlock the power of immunotherapy where it once failed — turning a terminal diagnosis into a longer, stronger fight for life.
Source: Keck Medicine of USC
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