Biomarkers predict patients with glioblastoma who will survive longer after treatment with cancer-targeting virus

  • Glioblastoma is a deadly brain cancer that suppresses the immune system and doesn’t respond well to available therapies
  • Researchers engineered a cancer-targeting virus that can be injected directly in glioblastoma tumors
  • Adding an immune booster to the virus increased the length of survival in a subset of patients and helped identify blood biomarkers in patients most likely to benefit

Researchers at The University of Texas MD Anderson Cancer Center have identified blood-based biomarkers that can help distinguish patients with glioblastoma who are most likely to live longer from novel treatment with an engineered oncolytic virus, Delta-24-RGD, that targets and eliminates cancer cells.

The study, published in Clinical Cancer Research, was led by Frederick Lang, M.D., chair of Neurosurgery and co-director of MD Anderson’s Cancer Neuroscience Program, and Chibawanye Ene, M.D., Ph.D., assistant professor of Neurosurgery.

“Identifying a biomarker of response after treatment allows us to identify patients who are responding to therapy early in their course, before definitive responses are seen on MRI,” Ene said. “This information will tell us who is most likely to benefit from additional doses of Delta-24-RGD to treat their brain tumor. Additional treatments with Delta-24-RGD could further activate the immune system in these patients to continue to fight the tumor, resulting in longer overall survival.”

What is glioblastoma and why is it hard to treat?

Glioblastoma (GBM) is one of the most aggressive and deadly forms of brain cancer, and it is notoriously difficult to treat. While many cancers respond to immunotherapy, the GBM tumor microenvironment is considered immunologically “cold.”

The GBM tumor microenvironment is surrounded by cells that suppress an immune response, making it difficult for immune cells to recognize or destroy cancer cells. Additionally, the blood brain barrier prevents many treatments from reaching tumors in the brain. Therefore, researchers have been focused on developing new treatments that are more effective.

What is an oncolytic virus and how does it help?

Researchers at MD Anderson, led by Juan Fueyo, M.D., and Candelaria Gomez-Manzano, M.D., professors of Neuro-Oncology, engineered the Delta-24-RGD oncolytic virus, which is designed to selectively infect and eliminate cancer cells without harming regular cells. The virus can be directly injected into GBM tumors, bypassing the blood brain barrier, and has previously shown antitumor effects in Phase I clinical trials.

Additionally, a small subset of patients had much better immune responses and prolonged survival when the virus was combined with immunotherapy, suggesting this approach has the potential to make these tumor microenvironments immunologically “hot.”

In this two-part Phase I TARGET trial, the researchers wanted to examine whether adding subcutaneous interferon gamma (IFN-γ), which also helps to boost the immune response, would improve the efficacy of the virus treatment in patients with recurrent GBM.

What were the results of adding an immune booster?

Patients in the trial who survived longest were those who received IFN-γ after treatment with the virus. Further analysis of blood samples taken two months after treatment revealed that patients who had the longest survival times also had higher levels of specific biomarkers that indicate a strong immune response, known as “immunological fitness.”

These results suggest that these blood-based biomarkers may help identify patients who have stronger immunological fitness and may benefit most from additional doses of the oncolytic virus.

The researchers continue efforts to explore the benefits of this therapeutic approach. There is an ongoing clinical trial evaluating multiple doses of mesenchymal stem cells loaded with Delta-24-RGD in patients with recurrent GBM.

***

This study was supported by the Cancer Prevention and Research Institute of Texas (CPRIT), the National Cancer Institute and the National Center for Advancing Translational Sciences of the National Institutes of Health, The Broach Foundation for Brain Cancer Research, The Elias Family Fund for Brain Tumor Research, Jason and Priscilla Hiley, The Curefest Brain Cancer Research Fund, Pamela and James Harris, the Gene Pennebaker Fund for Brain Cancer Research, the Ira Schneider Memorial Cancer Research Foundation, the Sweet Family Brain Cancer Research Fund, the Dr. Marnie Rose Foundation, Peter and Christina Gold, Sorenson Brain Tumor Research, and the TLC2 Foundation. A full list of collaborating authors and their disclosures can be found with the full paper.

Identifying a biomarker of response after treatment allows us to identify patients who are responding to therapy early in their course, before definitive responses are seen on MRI. This information will tell us who is most likely to benefit from additional doses of Delta-24-RGD to treat their brain tumor. Additional treatments with Delta-24-RGD could further activate the immune system in these patients to continue to fight the tumor, resulting in longer overall survival.

Chibawanye Ene, M.D., Ph.D.

Neurosurgery