Biomarkers, Oncolytic Viruses, and the Promise of Personalized Treatment for Glioblastoma

For patients diagnosed with glioblastoma (GBM), the prognosis has long been grim. Surgery, chemotherapy, and radiation remain the standard of care, yet these tumors almost always return. Chibawanye I. Ene, MD, assistant professor of Neurosurgery at The University of Texas MD Anderson Cancer Center, has spent nearly 15 years searching for a better answer. His focus: oncolytic viruses, and specifically the Delta-24-RGD virus, which was engineered at MD Anderson to selectively destroy tumor cells while leaving healthy tissue intact. In a recent study published in Clinical Cancer Research, Ene and colleagues identified blood-based biomarkers that may predict which patients with GBM are most likely to survive longer following treatment with this cancer-targeting virus.^1,2 Targeted Oncology spoke with Ene about the findings and what they mean for the future of GBM care.

What drew you to glioblastoma research, and specifically to oncolytic viruses?

"I honestly wasn't satisfied that surgery and then chemotherapy and radiation was not enough," Ene said. "These tumors typically tend to come back, and so we've been in the lab looking for other ways to slow these tumors down and keep them from coming back."

When he arrived at MD Anderson as a fellow, he began working alongside Frederick Lang, MD, on the Delta-24 oncolytic virus—not only to make it work better, but to understand which patients it was working for. "That's how I started working with Dr Lang on finding ways to make the oncolytic viruses work better, but importantly, figure out who it's working better for, so we can essentially find those patients and treat them with more Delta-24."

The virus itself has a compelling origin story. Delta-24-RGD is derived from the adenovirus, a cause of the common cold. Researchers Juan Fueyo, MD, and Candelaria Gomez-Manzano, MD, professors of Neuro-Oncology at MD Anderson, modified it so that it replicates exclusively in tumor cells. "They modified this virus so that it only infects tumor cells," Ene explained. "The common cold infects normal cells, but they modified it and mutated it in a way that it only affects and replicates in tumor cells. And what that means is, when we put the virus in the tumor environment, it doesn't really affect normal cells. It only infects tumor cells, expands, and then the tumor dies." The body's immune response to the virus adds another layer of benefit—what Ene calls a "bystander effect." When the immune system recognizes the virus as a pathogen, it sends cells to attack, and those immune cells also identify nearby tumor cells as targets.

What was the focus of this particular study, and what were the key findings?

The research examined samples from the TARGET trial (NCT02197169), a phase 1 clinical trial that compared patients who received Delta-24 alone with those who received the virus in combination with subcutaneous interferon gamma (IFN-γ), an immune-stimulating agent. The rationale was straightforward: if the virus works by releasing tumor antigens and activating an immune response, adding an immune booster might amplify that effect.

"We felt that if we gave an additional boost of an immunotherapy that may help the virus work better and improve survival," Ene said.

The results bore that hypothesis out. "What we found was the patients who lived the longest were the patients who received that immune stimulating therapy on top of the virus." The team then went further, using single-cell RNA sequencing and antiviral antibody testing on blood samples drawn 2 months after treatment to identify what distinguished long-term survivors from those who did not live as long. Crucially, all of this work was done outside the tumor—in the blood—making it far more feasible than repeat brain biopsies.

"For me, that is important, because a lot of times it's very difficult to access the tumor in the brain. Unlike other cancers in the body, it comes with a lot of risk,” Ene said.

Two specific biomarkers emerged. The first, identified via single-cell RNA sequencing, was an activated T-cell subtype: a CD8-positive natural killer T cell. The second was the patient's antiviral antibody response: "Anyone who can mount a good antiviral response, based on how much antibodies their bodies produce, specifically to Delta-24, seem to live longer after this treatment." These markers now form the basis for a prospective biomarker strategy being incorporated into ongoing Delta-24 trials.

What are the implications for clinical decision-making?

Ene sees these findings as the foundation for a more personalized treatment approach in GBM. Rather than waiting for changes to appear on MRI, which often reflect late-stage events, clinicians may be able to use blood-based markers to intervene earlier.

"A lot of the changes that happen on the MRI…are late findings. What may be happening, especially with immune therapies like Delta-24, are systemic. They're in the blood. And if we can catch them early, I think we can actually start identifying patients who may benefit from additional doses of Delta-24,” Ene said.

Conversely, patients who do not show early biomarker response could be redirected to a different treatment altogether. The broader goal, he said, "is to find which treatments our patients will benefit the most from and put them in that situation where they will actually benefit from that treatment."

The delivery of the virus is also evolving. While the TARGET trial administered Delta-24 directly into the tumor via catheter, an ongoing trial is exploring intraarterial delivery: threading the virus through the blood vessels that selectively feed the tumor, a technique adapted from stroke intervention. This approach allows for more widespread distribution of the virus across the tumor, and patients in this trial receive multiple doses over several months.

"We're now doing trials where we're giving more Delta-24, but it would be very helpful to say this patient showed that early marker for long-term survivors and will benefit from additional doses."

What would you say to community oncologists following this research?

For physicians in community practice, Ene offered a message of cautious optimism alongside a concrete clinical takeaway. "I think there are treatments in the horizon, still in clinical trials, that are showing promise for [GBM]," he said. When patients with a new GBM diagnosis search the internet, they often encounter discouraging information about prognosis, and it's important for their physicians to offer a fuller picture of where the field is headed.

On the practical side, Ene urged community oncologists to expand their thinking beyond MRI interpretation when monitoring patients on immunotherapy trials. "When we're drawing blood work, 3 months, 6 months down the road, we should start incorporating markers, not just for Delta-24, but for other immunotherapy trials—start incorporating markers that may indicate response, especially in the blood. That will be the big thing I would pass on to our community physicians: We should start thinking about looking for markers of response through your traditional blood draw that doesn't require a brain biopsy, which is risky, but doable."

REFERENCES

1. Ene CI, Singh S, Venkataraman T, et al. Systemic immune correlates of long-term survival after Delta-24-RGD based on the Therapeutic Adenovirus for Recurrent Glioblastoma Effect Trial (TARGET). Clin Cancer Res. 2026 Jan 29. doi: 10.1158/1078-0432.CCR-25-3566. Epub ahead of print. PMID: 41609523.

2. Biomarkers predict patients with glioblastoma who will survive longer after treatment with cancer-targeting virus. News release. MD Anderson Cancer Center. February 10, 2026. Accessed March 12, 2026. https://tinyurl.com/576skuhh