Research tests light-activated treatment for brain cancer
The catheter glows pink when the laser switches on. Inserted into the cavity where a brain tumor used to be, it bathes the surrounding tissue in light for roughly 30 minutes. This activates a cancer-killing drug circulating in the blood, targeting microscopic tumor cells that no surgeon can see.
"Think of it as a technique to clean up the tumor you leave behind after surgery," said John Rossmeisl, the Dr. and Mrs. Dorsey Taylor Mahin Professor of Neurology and Neurosurgery at the Virginia-Maryland College of Veterinary Medicine. "We never remove all the tumors because we can't see the microscopic tumors. The light will activate the drug circulating where the microscopic cancer cells are and hopefully kill them."
Rossmeisl, also associate department head in the Department of Small Animal Clinical Sciences, will lead clinical trials of this therapy at the Veterinary Teaching Hospital in Blacksburg this year.
When brain tumors resemble the normal brain
Approximately 12,000 Americans each year receive a diagnosis of glioblastoma, according to the American Brain Tumor Association. Despite surgery, chemotherapy, and radiation, most survive less than 18 months. Microscopic cancer cells that infiltrate healthy brain tissue beyond the visible tumor margins drive the cancer’s recurrence.
The challenge: Tumor tissue can be indistinguishable from healthy brain tissue.
"Sometimes you can clearly see a discolored mass that has a different texture or feel from the surrounding brain," Rossmeisl said. "One of the challenges with glioblastoma is that the tumor can look exactly like normal brain tissue. You can't tell the difference, which is why it's really difficult to remove those things — you have no idea where the border of the tumor is."
Testing a new treatment
The treatment pairs photodynamic therapy — a technique that uses light to activate cancer-killing compounds — with a novel nanoparticle drug developed by Joe Huang, an associate professor in the Fischell Department of Bioengineering at the University of Maryland.
Researchers observed that the nanoformulation of verteporfin, known as NanoVP, significantly increases both potency and tumor penetration compared to currently approved photosensitizers in preclinical studies. Its unique ability: It crosses the blood-brain barrier.
"The reason a lot of drugs don't work against brain cancers is that the blood supply to the brain excludes those drugs from getting in there," Rossmeisl said. "This will get in there. That's the reason he really wants to look at it in brain cancer."
Because NanoVP is based on verteporfin, a Food and Drug Administration-approved drug used to treat eye disease, researchers have confidence in its safety profile.
"Dr. Huang's compound, although novel, it's already approved for people, so we know it has a good safety profile," Rossmeisl said.
How the collaboration came together
A mutual connection fostered the partnership. Huang contacted Rossmeisl about testing the new drug formulation. Both previously collaborated with Graeme Woodworth, a neurosurgeon at the University of Maryland School of Medicine and director of the Brain Tumor Program.
In November, Huang brought his research team to Blacksburg to walk through the clinical workflow at the Veterinary Teaching Hospital.
"We went through the clinical trial workflow — how it would actually work in the hospital — and did a pilot study and got some preliminary data," Rossmeisl said. "We're pretty much ready to go."
Industry partner Modulight Corporation provides the specialized laser systems. The company is currently running a human clinical trial of similar photodynamic therapy technology in Germany.
What the trial will test
The initial trial aims to establish optimal dosing protocols and exposure parameters in treating three to five dogs with any type of brain cancer. This phase is designed to inform future studies by identifying the safest and most effective approaches.
"This is kind of an all-comers study for dogs with brain cancer," Rossmeisl said.
The primary objective is to determine the safest and most effective dosing and light-exposure parameters, addressing questions not resolved in preclinical studies.
"We want to learn how the new drug is processed in the body and what the ideal dose is," Rossmeisl said. "We're also seeking to determine how long the drug should be exposed to light for maximum efficacy. These are the main questions the trial is designed to answer."
Why dogs matter for human medicine
Dogs develop brain tumors spontaneously, making them valuable research partners for understanding how treatments perform in naturally occurring disease rather than artificially induced conditions.
"Mice aren't people, they process drugs differently," Rossmeisl said. "This will help us answer fundamental questions we need to know before we can answer how well this actually works against the tumor."
Pet owners whose dogs have brain cancer can enroll in the study and receive standard medical care plus the experimental photodynamic therapy.
In an announcement about the collaboration, Huang emphasized the dual benefit: "Our goal is to improve the lives of both humans and our best friends. This work allows us to push brain cancer treatment forward while giving families and their pets hope in the process."
A potential bonus: Seeing the invisible
Rossmeisl currently uses fluorescent-guided surgery to distinguish tumor from healthy brain tissue. He wears specialized eyewear that makes certain dyes glow when absorbed by cancer cells. But existing agents have limitations.
"Many of the currently available fluorescent agents do not entirely target cancer," Rossmeisl said. "Sometimes, the part of the brain reacting to the disease highlights itself, but we don't want to remove that."
NanoVP might do double duty. Beyond killing cancer cells after surgery, it might also help surgeons visualize tumor margins during the operation.
"His agent might be able to add specificity to fluorescent-guided surgery, so we may actually be able to see where those microscopic cells are," Rossmeisl said. "That's something we're also going to try to get preliminary data on. We don't know if that's going to work or not."
Path to human trials
The Virginia Tech team will use canine trials to establish safety and dosing parameters before advancing NanoVP to human trials in the United States.
"Once we answer those basic questions, our plan is to submit an NIH R01 grant to answer the question: How well does it actually work against the tumor?" Rossmeisl said.
"Photodynamic therapy has been tried for brain tumors for a while," he aid. "There are a lot of photosensitizing agents and techniques that have been tried. We're trying to combine this novel catheter with the novel drug to make it better."
For now, the work begins in Blacksburg — one pink light, one patient at a time.
Dog owners interested in learning more about the clinical trial can contact the Veterinary Clinical Research Office at the Veterinary Teaching Hospital.
