The Dogs in This Clinical Trial May Change How We Treat Brain Cancer in Children

There is a type of brain cancer in children called high-grade glioma. Patients with this diagnosis rarely survive a year after it is made. Radiation therapy slows the disease but does not eliminate it. The tumors come back. And despite decades of research, medicine has not yet found what to add to the treatment to change that outcome in a meaningful way.

A clinical trial currently enrolling at Colorado State University's College of Veterinary Medicine and Biomedical Sciences may represent a step toward that answer. The patients in the trial are dogs. The disease they carry is naturally occurring, biologically similar to the pediatric cancer it is being used to model, and the combination therapy being tested could eventually lead to a trial in children.

This is One Health in its most direct and consequential form.

What Is Being Tested and Why

The trial combines two treatment approaches that have not been used together in this context before.

The first is CAR T-cell therapy, a method for engineering a patient's own immune cells to make them more effective at identifying and attacking cancer. CAR T-cell therapy has produced remarkable results in blood cancers. In solid tumors, including brain tumors, it has been far less effective, and the reason is the tumor itself.

Brain tumors create what researchers describe as an immunosuppressive microenvironment. CAR T cells can reach the tumor site but then encounter conditions that prevent them from functioning properly. They fail to propagate, they die off, or their effectiveness is blunted before they can do significant damage to the cancer. Getting around that microenvironment barrier is one of the central unsolved problems in solid tumor immunotherapy.

The second component of the trial is verdinexor, an oral cancer drug that works by trapping tumor-suppressing proteins inside the nucleus of cancer cells, where they force those cells to die. The hypothesis driving this trial is that verdinexor may do more than directly target cancer cells. It may also alter the tumor microenvironment in a way that makes it more permissive for CAR T cells to function, potentially solving or partially solving the problem that has limited CAR T therapy in solid tumors.

"Using verdinexor could not only make the tumor cells more susceptible to the CAR T cells, but we hypothesize it also affects the tumor microenvironment," says Charlotte Feddersen, MD, PhD, a pediatric hematology and oncology fellow at the CU Anschutz School of Medicine who is collaborating on the trial. "One of the problems we run into when we use CAR T therapy for brain tumors is that we can get the CARs to the tumor, but they encounter an immunosuppressive environment where the CAR T cells don't propagate, or they die, or they're not as effective. There's a huge push to find ways to make that tumor microenvironment more permissive."

Why Dogs and Why Now

The trial is being led by Steven Dow, DVM, PhD, and Stephanie McGrath, DVM, at CSU's College of Veterinary Medicine and Biomedical Sciences in Fort Collins, and it is enrolling dogs with naturally occurring brain cancer.

The use of companion dogs in cancer research is not a shortcut or a substitute for a better model. Dogs develop brain tumors spontaneously, not because they were induced or genetically engineered to do so in a laboratory. The biology of those tumors, the way they respond to radiation, the way they recur, the microenvironment they create, mirrors what clinicians see in pediatric patients with high-grade gliomas closely enough to make canine patients a genuinely informative model for developing new treatment approaches.

"What we see in both canines and pediatric patients is that these tumors respond to radiation, but it doesn't make them go away completely, and then they come back," Feddersen says. "We need something else to add to the treatment, but decades of research have not yet revealed what that is."

The trial structure mirrors standard pediatric care as closely as possible. Dogs receive upfront radiation therapy, which is the current standard of care for canine brain tumors, and then receive the experimental CAR T-cell therapy afterward. That sequence intentionally replicates what pediatric patients typically experience, which makes the canine data more directly applicable to a future human trial.

The Logistical Challenge

One of the practical difficulties this trial has had to solve is timing. Creating a CAR T-cell therapy from a patient's own cells is not a quick process. It typically takes two to three weeks from the time cells are collected to the time the therapy is ready to administer. Dogs with brain cancer often present when the disease is advanced or highly symptomatic, which makes it difficult to stabilize the patient long enough to complete that process.

The upfront radiation approach addresses this directly. By beginning with radiation, the team buys time for the CAR manufacturing process while simultaneously providing the standard of care the dog would receive regardless. It is a practical and clinically sound solution to a real enrollment and treatment challenge.

What Success Would Mean

Feddersen is explicit about what she is hoping to demonstrate and why it matters for pediatric patients specifically.

"We don't currently have in-house manufactured CAR T cells at this institution for pediatric brain tumors, specifically pediatric high-grade gliomas, which is a really underserved population," she says. "These patients rarely survive a year after their diagnosis. There have been some promising CAR T cell trials at other institutions, and I have some evidence that this CAR works on brain tumors in lab-based animal models. If we could see that it had some effect in dogs, that would go a long way toward providing preliminary effectiveness and safety data to help us be able to offer this to patients at our institution."

That framing is important. This trial is not trying to cure canine brain cancer in isolation. It is trying to generate the safety and effectiveness data that would justify and support a human clinical trial. The dogs being enrolled in Fort Collins are not proxies. They are patients with a real disease receiving real treatment. But the data their treatment generates could eventually be the evidence that opens a new option for a child diagnosed with a cancer that currently offers very little hope.

The Larger Picture

This trial represents exactly what the One Health framework is supposed to produce. A pediatric oncologist sees a gap in available treatment options for the most vulnerable patients. A veterinary oncology program at CSU has the infrastructure, the expertise, and access to a naturally occurring animal model that closely parallels the human disease. A collaboration forms. A trial is designed that benefits the animal patients enrolled in it while simultaneously building the evidence base for a future human trial.

The dogs in this study have brain cancer. They would receive radiation with or without the trial. What the trial offers them is access to an experimental combination therapy that may improve their outcomes, along with the kind of careful monitoring and expert oversight that a clinical trial provides. What their participation offers the children who will come after them is harder to quantify but no less real.

The trial is currently enrolling at CSU's College of Veterinary Medicine and Biomedical Sciences in Fort Collins, Colorado.

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