Dr. Mahua Dey is an associate professor in the Department of Neurological Surgery and the director of the surgical neuro-oncology program in the University of Wisconsin School of Medicine and Public Health. She specializes in the surgical management of both benign and malignant brain tumors.
In 2023, Dey was nominated for a Wisconsin Alumni Research Foundation (WARF) Innovation Award for her work towards a personalized therapeutic cancer vaccine to treat glioblastoma — one of the the deadliest forms of cancer. WARF, which serves as the technology transfer office for UW–Madison, has supported faculty across the University of Wisconsin School of Medicine and Public Health through grants, research facilities, and the patenting and licensing of breakthroughs that have benefited the world.
How do you describe your field and specialty?
I am a neurosurgeon-scientist specializing in the surgical management of brain tumors. I operate on patients with brain tumors and then study the malignant tumors in my lab, with the goal of developing novel immunotherapies for malignant brain cancer. One of the main focuses of my lab is development of a therapeutic vaccine for glioblastoma, the most common and most aggressive type of malignant brain tumor. We use surgically removed brain tumor samples to develop this personalized, genetically modified therapeutic vaccine, which will not prevent primary brain cancer but will hopefully provide a cure for patients who develop it.
Why were you drawn to surgical management of brain tumors?
I have always been fascinated by the brain. It’s the organ that makes us human, yet we understand so little about it. As a surgeon, I have the privilege of studying this complex organ in the operating room in a way that is impossible in any other setting. I can observe how a tumor is connected to surrounding tissues, including brain regions responsible for vital functions, which helps me understand more about tumors’ growth, biology and impact on brain function. I find working on complex problems very rewarding, and malignant brain cancer is the hardest disease to treat, with no therapeutic breakthrough so far.
Describe glioblastoma, the disease you are currently studying in your lab.
Currently, there is no effective treatment for glioblastoma. The tumor recurs in all patients after a certain period of disease control, and most patients succumb to the disease within two years. Unlike other cancers, this one essentially robs patients of their own selves: their personality, their ability to think and speak clearly and perform daily activities. Since glioblastoma is a disease primarily affecting older adults, the aging immune system also plays a role in the overall poor prognosis.
How does the therapeutic vaccine work?
Our GIFT-7 personalized glioma vaccine is a live vaccine containing genetically modified tumor cells with engineered fusokines, which are proteins that we have designed to boost aging immune systems and train them to recognize a cancer threat. We create a fusokine by combining two cytokines (signaling proteins) into a single molecule. Improved signaling helps produce a robust anti-cancer immune response. Using this approach in the mouse model, we have been able to completely clear glioblastoma from the brain. The cured mice also generate immunological memory; if they are challenged again by the same tumor, their immune systems promptly reject it.
What is the potential impact of the vaccine, on patients’ lives and within the field of cancer research?
If successful, this will be a game changer for glioblastoma patients. Current median survival for the disease is between nine and twelve months and it has a recurrence rate of almost 100%. We can’t stop people from getting glioblastoma, but if the vaccine works in patients as it does in mouse models, we will essentially stop the disease from coming back.
We hope this vaccine may one day be adapted to treat other cancers in aging adults, since the basic mechanism of the vaccine is to boost one’s own immune system to target the cancer cells.
Is this vaccine close to a clinical trial?
Our initial pre-clinical work showed that the vaccine is highly effective in multiple mouse models of glioblastoma. Since then, we have done in vitro testing of the human version of the vaccine and have found that patient-specific vaccines activate patients’ T-cells (protective white blood cells) for cytotoxic activity, or the ability to attack cancer. Now we are working on achieving good manufacturing practice (GMP) standards, ensuring quality and safety for human use. Once we create a GMP-grade vaccine, we will be ready to file for an investigational new drug application with the Food and Drug Administration to start a Phase I clinical trial. Our goal in that trial will be to evaluate the vaccine’s safety and determine dosage.
What are some of the unique challenges you face?
I get to know my patients and their families really well during their journeys, and eventually the treatments fail them. Many times, I take that as a personal failure, and it can be very demoralizing. However, I am very fortunate that many family members stay in touch with me even after the patient passes away, which makes me think that maybe I was able to make some difference in their lives. Another challenge of developing translational therapies is the complex coordination needed to bridge multiple disciplines. Over time I have learned to identify key collaborators and intentionally develop more in-depth work with them. Our vaccine work is a successful example of this focused, small-team strategy.
What motivates you to keep going in the face of setbacks?
If a goal doesn’t scare me and keep me up at night, then it’s not really a worthy goal. Science can be brutally heartbreaking at times. We do what we do because there are patients whose lives are cut short by this devastating disease. Our goal should always be to find a cure, and if we fail in that, we will at least end up increasing the survival rate.
How does your clinical practice inform your research, and vice versa?
To me, the role of surgeon-scientist is the best of all worlds — science meets humanity. As a surgeon, I remove brain tumors. As a scientist, I formulate and test hypotheses on what can be done to prevent this cancer from coming back. Each process feeds the other. Even though brain tumor patients face one of the worst cancer prognoses, they are often some of the most resilient and uplifting people I know. I find their courage and grace very motivational in my lab research.
Why is UW a great place to pursue your work?
UW is a complete ecosystem where one can take a basic science finding all the way to a clinical trial. When I was being recruited, I met with Dr. Jacques Galipeau, founding director of the Program for Advanced Cell Therapy. That meeting eventually led to a collaboration between our labs, and this vaccine is a direct result. I then had a serendipitous encounter with Jonathan Young, the chief scientific officer of WARF, and mentioned to him our very promising pre-clinical findings for the glioblastoma vaccine. WARF recognized the potential of our vaccine and the large unmet need for therapeutic development in the field of glioblastoma. This kind of multi-sector collaboration is a great example of what is possible at UW–Madison.
