Future of immunology: It’s all about balance
David M. Lee, Global Head, Immunology, Inflammation and Infectious Diseases at Roche Pharma Research and Early Development, shares personal insights from his experience as a physician and talks about how recent developments in immunology could potentially lead to new treatment approaches for patients with severe immune-mediated diseases.
Why did you decide to focus your medical and scientific career on immunology and rheumatology?
I grew up on a small dairy farm in a rural area of northern Minnesota. It was a wonderful experience that taught me a lot of lessons in life. It was, however, not exactly a bastion of science. The focus at high school was more on agriculture, welding and repairing small engines.
I became fascinated with immunology during my undergraduate studies at Stanford University in California, which had attracted many leading immunologists in the 1980s. I also had exposure there to basic laboratory research that was medically focused. I was enthralled with the idea of marrying my interests in science with contributing to society.
After completing MD and PhD degrees at Duke, I went to Brigham and Women's Hospital/Harvard Medical School in Boston for a medical residency and a rheumatology fellowship. From 2002-2010, I treated patients one day a week, while continuing to pursue my research in rheumatology.
I want the international community to know that Roche is expanding its R&D in immunology, including some exciting clinical programmes.
What type of rheumatological conditions did you see as a physician and what was “state of the art” in treating patients at that time?
Most patients who came to me had rheumatoid arthritis, an immune-mediated disease that attacks the joints and can disfigure patients so badly that they are unable to use their hands or feet. Prior to the late 1990s, many of the drugs we had at our disposal were relatively toxic. They reduced the symptoms but had considerable side effects.
Then along came a new generation of biological drugs, the TNF inhibitors. Some patients had an immediate response and experienced dramatic improvements. However, many others did not respond at all. A few even had life-threatening bacterial infections, which illustrated the risks of this type of immune suppression. So while it was truly exciting to see the potential of this new biological therapy, it was also frustrating as a physician to only help less than half of the patients.
You can’t read about these immune-mediated diseases in a textbook and understand their impact on a patient’s quality of life.
How would you describe the Roche strategy in treating rheumatological/ immunological diseases?
In broad terms, our strategy is based on restoring immune balance. The approach to immune-mediated diseases in the past has been on simply suppressing the immune system. Now that we know a lot more about the immune pathways, both “accelerators” and “brakes”, and how they drive the immune system responsiveness, we hope to manipulate them in a more refined way to restore immune balance.
If we focus on immune pathways and develop treatments with this concept in mind, what’s very clear is that once we identify the right treatment to modulate a certain immune pathway, this often gives us an opportunity to treat multiple different immune-mediated diseases with a single drug.
Another major principle of our strategy is precision combination therapy. That means combining new therapies with existing ones that have demonstrated safety and efficacy, but perhaps for less than half of all patients. We have seen in infectious diseases and oncology that if you find a safe combination, you may get a synergistic efficacy boost. We hope to achieve that by combining new therapies for tissue-driven inflammation with established immune therapies.
How do you see the future of immunology treatments?
I’m not satisfied with the response rate from today’s treatments, or the fact that many patients who do respond have only incremental improvements. I think our patients deserve better. We need to set the bar high by aiming for complete remission. It will be a challenge, but science is progressing at an unprecedented pace.
In fact, there has never been a better time for discovery and early development in immune diseases. A number of recent substantial advances in our understanding of human immune pathways give us new ways of getting more selective treatments for patients, and enable us to enter these very heterogeneous populations with a much higher degree of confidence.
By using the ‘accelerator’ and the ‘brake’ concepts of regulating the immune system, we can manipulate it in a more refined way.
How do your years of experience with patients influence your daily work?
It’s absolutely foundational. You can’t read about these immune-mediated diseases in a textbook and understand the impact on a patient’s quality of life. We want to focus our energy at Roche on developing drugs for immune-mediated diseases with the greatest unmet need.