In This Article
- Neurosurgery, gene, and cellular therapies work synergistically to provide personalized medicine
- CAR T-cell therapy harnesses the immune system by attaching to proteins on the surface of brain tumor cells. Neurosurgeons and oncologists are working to attach CAR T-cells to multiple pathways to treat glioblastoma, which is an aggressive brain tumor
- Cellular engineering has been used to transform a patient's own stem cells into dopamine neurons to treat their Parkinson's disease
- Liquid biopsy might allow neurosurgeons to eliminate an invasive brain surgery in some instances by performing a simple blood test
Bob S. Carter, MD, PhD, is the chief of the Department of Neurosurgery at Massachusetts General Hospital. He specializes in complex intracranial surgery and with a research focus that includes personalized cellular therapies. In this Q&A, Dr. Carter reflects on his time as the chief of neurosurgery, the intersection of neurosurgery and neuroscience research and personalized medicine with gene and cell therapies. Dr. Carter is also a 2021 Congress of Neurological Surgeons (CNS) honored guest.
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Q: As the Chief of Neurosurgery at Massachusetts General Hospital for nearly 5 years, how has your vision for the Department of Neurosurgery and the role of neuroscience research evolved over this time?
Dr. Carter: Increasingly, we see the interconnections among the various clinical departments that care for the patient with neurological disease. When the Departments of Neurosurgery, Neurology, Psychiatry and the Division of Neuroradiology came together to form Mass General Neuroscience in 2017, it was our common vision that by working together we could provide the best care for patients while also solving the most challenging translational neuroscience research questions. Mass General, as a single hospital, supports the largest research program in the U.S., and it is a reflection of our belief that the integration of clinical care and research will bring us cures faster, which is what we all want.
Q: What led you to practice neurosurgery and neuro-oncology? And what led you to clinical research?
Dr. Carter: Initially, I was inspired by the technical elegance of neurosurgery. It truly is a specialty where millimeters matter in terms of achieving the best outcomes. I found that research also demands precision reminiscent of neurosurgery: the planning and execution of an experimental protocol and the range of outcomes that depend on a high level of both mental and physical dexterity are similar to the planning that goes into providing a successful, complex surgery for a patient with a brain tumor. However, the important thing about research is that the potential benefit is much greater than even the very best we can do in the operating room for a single patient. If we can find a new and better way of doing surgery through research, or find a cure to a neurological disorder through research, we will impact many more patients as we share that newfound knowledge with the medical community.
Q: Does your research inform your surgery or vice-versa? How so?
Dr. Carter: Very much so. Some of our research work currently is looking at how we can better visualize a tumor during an operation using fluorescence. We believe that if we can enhance our visualization of the tumor, we will be able to achieve a better tumor resection. We are also studying ways that patients with tumors can provide critical information to allow us to characterize a tumor non-invasively. This is a line of research into a technique called liquid biopsy that might allow us to eliminate an invasive brain surgery in some instances by performing a simple blood test.
Q: What are the typical surgeries that you perform? Do you specialize in a specific type of neurosurgical technique?
Dr. Carter: I am a neurosurgical oncologist with a heavy emphasis on complex cranial operations. I currently treat patients with both benign and malignant tumors. There is a heavy technical component to our surgical procedures including 3D visualization and brain mapping to develop the safest access to the tumor. This use of technology extends to the operation itself. We attempt to augment the senses of the neurosurgeon using microscopic magnification, use electrophysiological monitoring to gauge the stress on neural pathways and function during the procedure and use "navigation", a tool that is used to allow the surgeon to have a 3D millimeter by millimeter resolution map of the brain as the procedure is being accomplished. Intraoperative MRI or intraoperative endoscopy greatly enhance our ability to target our region of interest during the procedure while it is happening. In some cases, we even have the patient remain awake and functioning during the operation. All of these techniques have one purpose, to create a safer procedure for the patient.
Q: What are some of the broad topics that you study as a clinical researcher?
Dr. Carter: I have long been interested in gene and cell therapy. The molecular revolution has made it possible for us to know more and more about the molecular "why" of how a disease occurs. We can harness this information to deliver precision medicine. Gene and cell therapy is an important result of this personalization of health care. I believe in the coming years we will see a tidal wave of new treatments related to these forms of molecular medicine. Surgeons will have an important role to play both in the conception and development of these treatments, but also in formulating the best way to deliver gene and cell therapies to specific regions of the central nervous system.
Q: CAR T-cell therapy research at Mass General is an area of focus. What makes this a promising immunotherapy for glioblastoma, which is notoriously difficult to treat?
Dr. Carter: Chimeric antigen receptor (CAR) T-cell therapy is an example of the personalized treatment that I described earlier. I developed my first CAR in 1995, and it has been astonishing and wonderful to see how far this treatment has come in 25 short years. The idea of CAR T-cell therapy is to specifically harness the immune system by engineering it to attach the cancer-causing proteins that are present on the surface of brain tumor cells. Our first-generation CAR T-cells were designed to attack only a single protein on the tumor surface, yet glioblastoma has the ability to switch from one cancer-causing pathway to another and can render ineffective any therapy that attacks only a single pathway. Working with colleagues Marcela V. Maus, MD, PhD, director of the Cellular Immunotherapy Program, and Bryan Choi, MD, PhD, a neurosurgeon, we are now engineering CAR T-cells that can mobilize the immune system to attach multiple pathways, trying to match glioblastoma step for step.
Q: Recently, the Departments of Neurosurgery and Neurology conducted a successful human stem cell therapy course for a Parkinson's disease patient. Can you give some insight into this treatment?
Dr. Carter: This is another example of personalized medicine. In Parkinson's the key dopamine-producing cells in the brain degenerate and create many problems for Parkinson's patients. With the cell therapy that we have designed, the goal is to re-instate continuous dopamine production in the brain by using skin cells that have been re-engineered to become first autologous stem cells, and then dopamine-producing cells. It is these dopamine-producing cells that are implanted into the patient. This has been one of the most complex and exciting scientific projects I have been involved with and highlights the power of cellular engineering for neurodegenerative disorders.
Q: What role do you see the Department of Neurosurgery playing in developing and implementing neuroscience-based therapies?
Dr. Carter: Ultimately, developing new treatments and new cures for our patients is our goal. My goal as Department chair is to create a foundation, some might liken this to a coral reef, whereby top physicians and nurses, scientists, students, allied professionals, can bring the power of our entire organization to tackle these problems as a team. When we talk about "neuro" therapies, we are really talking about what our neuroscience team can do together to improve the lives of our patients.
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