While immunotherapy has made a name for itself in the field of cancer care, researchers at the University of Colorado Anschutz Medical Campus are taking the treatment powered by the body’s own immune system to the next level.
Their work was the focal point of the fall 2024 Transforming Healthcare event, “The Future of Immunotherapy: Breakthroughs Beyond Cancer,” on Nov. 12, where the scientists shared their efforts to develop more effective, precise and personalized treatments for conditions, such as rheumatoid arthritis, type 1 diabetes and autoimmune neurologic diseases.
CU School of Medicine faculty featured at Transforming Healthcare – The Future of Immunotherapy: Breakthroughs Beyond Cancer:
- Leslie Berg, PhD: Berg is professor and chair of the Department of Immunology and Microbiology and director of the Human Immunology and Immunotherapy Initiative at the CU School of Medicine on the CU Anschutz Medical Campus.
- Aimee Pugh Bernard, PhD: Bernard is an assistant professor in the Department of Immunology and Microbiology at the CU School of Medicine.
- Peter Gottlieb, MD: Gottlieb is a tenured professor of pediatrics and medicine at the Barbara Davis Center for Diabetes at the CU School of Medicine and the holder of the Orr Family Endowed Chair in Adult Diabetes.
- Kristi Kuhn, MD, PhD: Kuhn is the Scoville Endowed Chair and head of the Division of Rheumatology and a professor of medicine and of immunology and microbiology at the CU School of Medicine.
- Amanda Piquet, MD: Piquet is the inaugural chair holder of the Céline Dion Foundation Endowed Chair in Autoimmune Neurology and director of the Autoimmune Neurology Program at CU Anschutz, where she also serves as the associate director of the Neuroinfectious Disease and Autoimmune Neurology Fellowship program.
To set the stage, Leslie Berg, PhD, described the immune system as a thermostat – one that requires a delicate balance to achieve optimal health – and immunotherapy as a way to activate or suppress the immune system when things go awry.
The immune system as a thermostat
When the immune system is working properly, the “thermostat” is at perfect balance, Berg said.
However, if the immune system is overactive – or the thermostat is too “hot” – the body can experience inflammation, leading to conditions like allergies, asthma, eczema and inflammatory bowel disease. In extreme cases, the body can experience autoimmune diseases, such as type 1 diabetes, rheumatoid arthritis, multiple sclerosis or lupus, she said.
Leslie Berg, PhD, provides an overview of immunotherapy.
Conversely, if the thermostat of the immune system is too “cold” or underactive, the system gets impaired. This makes it difficult to fight infections and can even lead to immunodeficiency. At either extreme, immunotherapy can help adjust the immune system into better balance, Berg said.
The ‘special forces’ of the immune system
Aimee Pugh-Bernard, PhD, provided an overview of the variety of cells that make up the immune system and how their malfunction leads to those cells attacking the body and causing autoimmune diseases.
The immune system trains billions of cells every day, said Bernard. Among these are the T cells and B cells, which she called “the special forces of the immune system.”
“Each T cell in our body and each B cell has a unique specificity, which means it goes after a unique and different target and piece of a pathogen in the body,” Bernard said. She pointed to the spike protein on SARS-CoV-2 (COVID-19) as one such example that these types of cells will target.
Aimee Pugh-Bernard, PhD, describes the role B cells play in the immune system.
When the body is functioning normally, the thymus – an organ where T cells mature – acts as a “university” for these cells, ensuring they aren’t autoreactive and won’t attack the body’s own cells. The problem is that these same cells can become autoreactive if that maturation process is disrupted. In some cases, these rogue cells end up attacking the body itself rather than an infection or pathogen, leading to autoimmune disease, Bernard said.
Scientists and doctors today better know the processes underway in B cells or T cells and can use them against these autoimmune diseases, Bernard said. In the case of T cells, for example, which recognize and kill infected cells, Bernard said:
“You can actually take the patient’s blood, isolate their T cells, reprogram their own T cells in the lab, then put them back in the patient.” The result? The T cells will go after a target of the provider’s choosing and then attack the rogue cells that are the root cause of the disease. This is the underlying process behind most immunotherapies for autoimmune disease.
A new gold standard in rheumatology
For rheumatologist Kristi Kuhn, MD, PhD, immunotherapy approaches have begun to show significant promise for the conditions she treats, making a difference for patients. The goal now, according to Kuhn, is to selectively turn off parts of the immune system while targeting specific inflammation-promoting chemicals in the body.
Transforming Healthcare is a community lecture series that showcases the extraordinary medical advancements and top scientists from the University of Colorado Anschutz Medical Campus. Presented by Chancellor Donald M. Elliman, each lecture examines a different timely topic in research, healthcare and innovation. Explore past events covering topics such as artificial intelligence and mental health here.
These advances have occurred alongside a better understanding about rheumatoid arthritis’s causal factors, including genes, environmental factors and even the gut microbiome, Kuhn said.
Kristi Kuhn, MD, PhD, walks attendees through the advances in treating rheumatoid arthritis using immunotherapy.
“Now we have five classes of effective therapies for rheumatoid arthritis,” she said. “We catch people early enough in their disease and can prevent them from having long-lasting joint damage and developing deformities. Immunotherapy has been really transformative for the field of rheumatology.”
A future without type 1 diabetes?
Around 2 million Americans have type 1 diabetes, where the immune system attacks insulin-producing cells in the pancreas. While immunotherapy is in the early stages in helping treat type 1 diabetes, it has already shown positive results in delaying the onset of symptoms, according to Peter Gottlieb, MD. Echoing Kuhn, Gottlieb said the promise of treating people before a disease starts – through early detection and better therapies – is a big leap forward for patients.
“For some of these patients, we’re getting three years of delay,” said Gottlieb. He mentioned that his colleagues both at CU Anschutz and across the country have even seen delays of eight to 10 years with no disease development. “For a little kid ... when you can push it off to late high school or later it really becomes a big deal,” said Gottlieb.
Peter Gottlieb, MD, explains the genetic component behind type 1 diabetes.
And at CU Anschutz, the future of treating type 1 diabetes is well underway. Gottlieb said the Barbara Davis Center for Diabetes opened an infusion center in April 2023 for patients in stage 2-type 1 diabetes – when blood sugar appears to be abnormal – to help delay the onset of symptoms and provide patients more time without needing supplemental insulin. The clinic is the largest center in the country using this medicine and the first in the Rocky Mountain region, already infusing 26 patients with this new therapy.
Gottlieb is optimistic about the future of immunotherapy in treating type 1 diabetes, saying the hope is to develop treatments that could prevent the need for insulin entirely.
New hope and awareness for rare autoimmune neurological diseases
Hope is also central to the final presenter, Amanda Piquet, MD. Piquet studies and treats rare autoimmune diseases that impact the brain and other parts of the central nervous system. Piquet said researchers' understanding of autoimmune neurologic diseases – and the antibodies responsible for causing them – have just emerged over the last two decades.
“This group of disorders was first discovered in 1965,” she said. “As time went on, we discovered a handful more throughout the years.” That was until the mid-2000s, Piquet said, when the field started rapidly expanding. Today, CU Anschutz is one of three centers that specializes in autoimmune neurology in the United States – alongside the Mayo Clinic and Thomas Jefferson University.
CU Anschutz, for example, is home to two ongoing clinical trials to better treat anti-NMDA autoimmune encephalitis. Attendees heard from Brooke Black, a patient with this rare condition, who experienced an entire range of symptoms from headaches, to hallucinations and seizures. Black was the first patient in the country to enroll in a new study for an experimental immunotherapy for anti-NDMA receptor encephalitis. Her journey back to health has been challenging, but she is grateful for a path forward and less uncertainty.
Patient Brooke Black discusses her anti-NMDA autoimmune encephalitis with Piquet and attendees.
Another condition Piquet treats is stiff person syndrome (SPS); her care for a high-profile patient, Céline Dion, led to a $2 million philanthropic investment from the Céline Dion Foundation. SPS is a rare autoimmune neurological disorder characterized by episodic and progressive muscle spasms and stiffness which can be triggered by noise, touch or emotional stress. As in the case of autoimmune encephalitis, the trigger for stiff person syndrome can often be a viral infection or benign localized tumors, which then cause the immune system to go awry and attack the brain.
The gift represents a turning point in the understanding of SPS and other autoimmune neurologic diseases, according to Piquet.
With a CAR T-Cell therapy clinical trial currently enrolling at CU Anschutz for SPS patients – alongside the many other immunotherapies discussed at the presentation – there is great reason for patients who’ve struggled with autoimmune diseases to have hope for a healthier future.
Watch the full presentation:
