Harnessing Electric Fields to Boost Immune Response Against Glioblastoma

Recent research conducted by scientists at Keck Medicine of USC has uncovered promising advancements in the treatment of glioblastoma, one of the most aggressive and deadly brain tumors. This study explores how combining Tumor Treating Fields (TTFields) therapy with immunotherapy and chemotherapy can significantly improve patient outcomes.

Glioblastoma typically carries a poor prognosis, with an average survival time of only about eight months following diagnosis, according to the National Brain Tumor Society. Traditional treatments, including surgery, radiation, chemotherapy, and immunotherapy, often fall short due to the tumor's ability to evade the immune system, partly because of the protective blood-brain barrier.

The innovative approach centers around TTFields, which deliver focused, low-intensity alternating electric fields directly into the tumor site. These electric fields disrupt the internal structures of cancer cells, hindering their division and growth. Patients wear electrodes on their scalp that generate these fields for approximately 18 hours each day, targeting tumors precisely.

A key finding from the study is that TTFields can attract T cells—white blood cells crucial for mounting immune responses—into and around the tumor. When boosted with immunotherapy agents like pembrolizumab, these T cells remain active longer and become more effective at attacking cancer cells.

"Combining TTFields with immunotherapy effectively primes the immune system to attack glioblastoma more successfully," explained Dr. David Tran, the study's lead researcher. "Our results indicate that TTFields can unlock the potential of immunotherapy in treating this challenging cancer."

The clinical trial analyzed data from 31 patients with newly diagnosed glioblastoma. Among them, 26 received TTFields along with chemotherapy and immunotherapy. Notably, patients with inoperable tumors, who have the fewest treatment options, experienced an approximately 13-month longer survival and exhibited stronger immune activation than those who had undergone surgical removal.

The methodology involved multiple sessions of chemotherapy combined with TTFields, with immunotherapy administered every three weeks over a span of up to two years. The combination therapy resulted in a 70% increase in overall survival compared to traditional treatments, highlighting the potential of this integrated approach.

Furthermore, the study emphasizes that the immunosuppressive environment created by glioblastoma—due to the blood-brain barrier and tumor's location—limits the effectiveness of many therapies. By initiating immune responses directly inside the tumor via TTFields, followed by immune checkpoint inhibitors like pembrolizumab, researchers aim to overcome these barriers.

The ongoing Phase III clinical trial aims to validate these findings in a larger, more diverse patient population. It is actively recruiting over 740 participants across multiple countries, including patients with various degrees of tumor resection.

This groundbreaking research suggests that leveraging electric fields to activate the immune system could fundamentally change glioblastoma treatment, offering hope for more effective options against this formidable cancer.