A conversation with Dr. Jeffrey Bluestone
Over the last two decades, new therapies that harness the power of the immune system have been developed to make cancers and debilitating autoimmune diseases more manageable and, in some cases, have led to cures. Dr. Jeffrey Bluestone is one of the pioneering scientists responsible for this shift, shaping the future of medicine through his relentless scientific curiosity and sharp focus on public impact. Pushing the boundaries of our understanding of immunology and immune tolerance for over 40 years, he has influenced the development of therapeutics for cancer and autoimmune diseases. Dr. Bluestone has received numerous awards for his work and was elected as a member of the American Academy of Arts and Sciences in 2006, the National Academy of Medicine in 2013 and the National Academy of Sciences in 2023. In his lab and through various past initiatives like the Parker Institute for Cancer Immunotherapy and the Immune Tolerance Network, and now, through his current venture, Sonoma Biotherapeutics, he has been at the forefront of developing new insights to control the immune response and deliver new transformative therapies to reset the immune system. His groundbreaking work in developing engineered regulatory T cell ( Treg ) therapies holds the promise of a new era in medicine and treatments for autoimmune diseases like rheumatoid arthritis and inflammatory bowel disease.
Jeffrey Bluestone, PhD, CEO and Co‑founder, Sonoma Biotherapeutics; A. W. and Mary Margaret Clausen Distinguished Emeritus Professor of Metabolism and Endocrinology, University of California San Francisco
What sparked your interest in biology and immunology? I have always loved science, especially biology. As a child, I spent many afternoons in the Museum of Natural History in New York City, studied all kinds of creatures and even spent a summer on a farm working with large animals. At Rutgers University, I worked in Dr. Robert Cousins ’ lab at Cook College on a senior honors project studying the basic biology of nutrition. I was blown away by the ability of science to identify the fundamental processes of the body and, more so, by the possibility that our work may eventually affect people ’ s lives. I entered a master ’ s program in virology at Rutgers, working on a polio-like virus found in mice. I enjoyed the research but wanted to paint on a bigger canvas. I had an opportunity to spend a summer in a cancer immunology lab at the Memorial Sloan Kettering Cancer Center ( MSKCC ) . That experience was transformational. Dr. Robert Good, an immunologist who ran the Sloan Kettering Institute, was among the first U.S. researchers to test the idea that the immune system could be harnessed to attack cancer cells. It was not yet a mainstream idea. Then, most of the focus was on developing treatments that directly killed cancer cells, like radiation or chemotherapy. However, inspired by the immense power of the immune system, I decided to play in this sandbox, so I entered the MSKCC PhD program at Cornell Graduate School of Medical Science to focus on cancer immunology. Dr. Good and others built on the anecdotal data from the studies by Dr. William B. Coley, a surgeon who operated on cancer patients in the late 1890s. Aseptic techniques weren ’ t very good then, and some patients developed infections, which, surprisingly, led many of their cancers to melt away. Dr. Coley went on to intentionally infect cancer patients with bacteria — pretty scary — but quite effective in some patients. These observations foreshadowed the field of immunotherapy and the concept that boosting the immune system could fight cancers. I was encouraged by the possibility of using the immune system to fight cancer but was struck by the hit-or-miss nature of the effects, with most cancers resistant to immune-mediated destruction. I focused my PhD on the idea that tumors might suppress the immune response by changing the microenvironment to inhibit tumor immunity. It took decades, but, finally, we and others showed that cancers were exceptional at shutting down the immune response by directly engaging the anti-tumor cells, known as checkpoints, and indirectly recruiting professional suppressor cells. These discoveries led to research on immune tolerance, where I have spent the rest of my career. How did your research change the way we understand the immune system? Immune tolerance is the ability of the immune system to respond to invaders while not attacking its own tissues — the fundamental cause of autoimmune diseases. My PhD work highlighted that the immune system had multiple mechanisms to block self-reactive immunity and that tumors were derived from one ’ s own tissues. So, it seemed logical that if the immune system could control anti- tumor responses, the reverse must also be true: Autoimmunity resulted from the breakdown of immune tolerance.
“ There are two sides to immune tolerance: inducing it and breaking it. ”
2
Made with FlippingBook flipbook maker