Since the very beginning of the human race, cancer has stood as one of the most formidable global health challenges. Casting a dark shadow over human mortality, this complex group of diseases continues to claim the lives of millions worldwide — affecting people of all ages, races, and socioeconomic backgrounds. Standard methods, such as radiation and chemotherapy, frequently have serious drawbacks, including adverse reactions and an inadequate level of accuracy. Dr. Michel Sadelain, M.D., Ph.D., has dedicated his life to changing the cancer narrative.
As opposed to cytotoxic drugs that directly kill pathogens or mutant cells, immunotherapy functions by activating the patient’s own immune system to eradicate the pathogens or mutant cells. Immunotherapy has seen revolutionary advancements in recent decades thanks to world-renowned immunologist Dr. Sadelain.
Born in Paris, France in 1960, Dr. Sadelain has always had a desire to explore the unknown. He received a medical degree in 1984 from the University of Paris and went on to earn a Ph.D. in Immunology at the University of Alberta in Canada in 1989. His postdoctoral stint at the Massachusetts Institute of Technology’s Whitehead Institute for Biomedical Research heralded an interest in a new, unfolding branch of genetic engineering. His glittering academic career would later form the bedrock for his seminal work in immunotherapy. In 1994, he moved to Memorial Sloan Kettering Cancer Center in New York City, where he founded the Center for Cell Engineering and developed therapies that would change the face of cancer treatment.
The basis of Dr. Sadelain’s research is CAR T-cell therapy, a new approach in the field of immunotherapy. The process starts with removing a patient’s T-cells, a type of white blood cell that is vital in fighting infection from the patient’s body. These T-cells are then genetically engineered in order to express on their surfaces a chimeric antigen receptor (CAR). A synthetic protein, the CAR recognizes and then binds to specific antigens on tumor cells. Once engineered, the T-cells are expanded to large numbers and re-introduced into the patient’s bloodstream. These “living drugs” then circulate through the body, seeking out and destroying cancer cells with unprecedented precision.
Dr. Sadelain’s innovations have been instrumental in taking CAR T-cell therapy from a theoretical concept to a clinical reality. His work first brought in critical improvements in CAR T-cells through the addition of costimulatory domains, enhancing the cell’s potency, durability, and survival in the body. The changes have increased significantly in the effectiveness of the treatment to date, allowing T-cells to wage a sustained attack against the tumor cells and reduce the risk of recurrence. In addition, Dr. Sadelain addressed crucial safety concerns related to off-target effects and cytokine release syndrome, a life-threatening immune response associated with CAR T-cell therapy.
CAR T-cell therapy has been most successful in the treatment of blood cancers, including Acute Lymphoblastic Leukemia (ALL). Patients in clinical trials with advanced-stage or treatment-resistant cancers have seen remarkable remission rates, with some achieving long-term survival. A May 2021 study examined long-term follow-ups from children with relapsed ALL who had been treated with CAR T-cells as part of a clinical trial. More than half of the children went on to receive a potentially curative stem-cell transplant and approximately 60% of those children were still alive five years later without their cancer coming back or the children experiencing any disease-related problems. These outcomes have provided hope to patients who had exhausted all other options, highlighting the transformative potential of CAR T-cells.
In addition to expanding the therapeutic reach of CAR T-cells, Dr. Sadelain is working to overcome the logistical and economic hurdles that surround the therapy. Manufacturing CAR T-cells is a specialized process, requiring sophisticated facilities and considerable resources; the treatment is consequently out of reach for many patients. He has taken the lead in the work of streamlining production methods, reducing costs, and developing universal CAR T-cells that would be used “off-the-shelf,” without the need for individual patient customization.
Dr. Sadelain’s seminal contributions have earned him global recognition. He was awarded the 2024 Breakthrough Prize in Life Sciences, one of the most prestigious honors in biomedical research. His additional accolades from just this year include the Canada Gairdner International and the Warren Alpert Foundation Prize. Further sealing his stature among professionals in cancer research studies, Dr. Sadelain was recently appointed Inaugural Director of the Columbia University Initiative in Cell Engineering and Therapy. In these roles, he has continued to spearhead innovative efforts in immunotherapy, leveraging a multidisciplinary approach toward collaborative boundaries.
Dr. Sadelain graciously agreed to be interviewed by me. Below are excerpts from our conversation:
When and where did your passion for life sciences originate?
“In high school, I liked everything. Whether it was languages, history, philosophy, or science — I loved it all. But I went to school in France where they required students to pick specialties in grades 10, 11, and 12. Nowadays, I think they only specialize in grades 11 and 12 because schools realized that specializing too early is not fair — most students don’t know what they want to do with their lives yet. But in my time, you had to choose. So I chose the math section. I probably would have been in the Bronx Science section of my school. There was a different section that was for biology, but I liked exploring everything and didn’t want to be confined to one topic. Philosophy was one of the things I liked the most — you don’t just study classical authors but use logic. When I ended high school, I wanted to know more about how our mind works. In that sort of bizarre, unintentional way, I got interested in medicine. I thought it would be a great profession where you’re supposed to do good, you’re supposed to help people. So I went to medical school; in the beginning I thought I would go to neurology. But then, things happen. I got interested in something I didn’t even know existed in high school, which was immunology. I think I was attracted to complexity. Of course, any area of biology is complex, but immunology seemed to be a place where there were such wild concepts. And so my plan drifted from the human mind to the human body and ultimately to immunology.”
You have an extensive educational background. At what point in your life did you decide not to pursue clinical work but rather focus on research? Why?
“It’s a very tough decision and a question that weighs on a lot of people with medical degrees. For some, it’s easy. A common misconception is that if you have a medical degree, you’re going to see patients. But sometimes doctors like myself deviate from the common path and do something else. I like working with patients but it was the medicine that really became my passion. To me, the doctor provides the medicine of today. And my job is to invent the medicine of tomorrow.”
What personal passions or values drive you to push forward in your research?
“Fighting disease is to improve the health of mankind. For me, there’s truly nothing more inspiring than that. The research, though, was to go to places where no one has gone before. Whether it’s Neil Armstrong exploring the moon or Christopher Columbus sailing to North America — it’s all an adventure of discovery. I think that’s really one of the most exhilarating things. I thought that there could be someone applying new principles and technologies to cure a disease that couldn’t be cured before. And I thought that person could be me.”
What has been the most challenging aspect of your work and how have you worked to overcome it?
“You need thick skin to do this. You really have to be strong in your mind. Research is about trying and failing — if it’s easy, someone else has done it before. If you’re tackling the unknown, you’ll try things and they will fail. Not getting the results you wanted can be unexpected, but if you learned something new, is it really a failure? To do research, you have to have the right approach, the right method, and the right attitude. Nobody had ever engineered a T-cell before. I had colleagues that told me, ‘It’s a clever idea, but you’re wasting your time.’ I had to think twice that maybe they could be right — maybe engineering T-cells was the wrong trail to blaze. It’s difficult when the most intelligent people around you are saying your idea is too complicated and will never work out. It’s hard to recruit people to build up a team, and it’s hard to find money. But one way or another, you have to convince people that your experiment is worth their money — you have to overcome the roadblocks and skepticism. The challenges come in a multitude of forms. But what makes me a researcher is that I believed in my idea. And it definitely paid off.”
You were recently awarded the prestigious 2024 Breakthrough Prize in Life Sciences. What does that recognition mean to you?
“It’s very flattering to be awarded such a prize, especially when you see the Nobel laureates who are on the jury. It’s humbling that, out of so many options, it was my work that they chose. The people who started the Breakthrough Prize are a group of very wealthy people in California — like Yuri Milner, Sergey Brin, and Mark Zuckerberg. Their mission, specifically through this prize, was to showcase today’s scientists to society. We always hear about singers, actors, and athletes, but rarely about scientists. The goal was to make the people who are behind the discoveries we all love more visible. A prize can’t begin to compare to the reward that is saving a human life. But it told the world that this is good, this works. It’s true, it’s real, it’s impactful. And most importantly, it can save lives. It tells all the people who were brave enough to work with me that it was all worth it. I say brave, because in the years where we weren’t sure if it would work, they believed that it could and dedicated all their time to it.”
You created the ‘Living Drugs’ documentary. How did that come about? What was its purpose?
“Two years ago, I was talking to a writer at The New York Times and she kept asking: ‘Where’s the drugs?’ What she struggled to understand was that the T-cells are the actual drug, which is what makes it so revolutionary. People too often associate drugs with pharmaceutical pills. However, in T-cell therapy, the T-cells come from the patient. Using genetic modification, we introduce a CAR into the T-cell, multiply it, and then give it back to the patient’s body. The CAR T-cell is alive — it divides, multiplies, and attacks the patient’s cancer cells. What we created were living drugs. And that’s where the documentary was born. It featured interviews with those that contributed to this discovery, like Dr.Isabelle Rivière, and patients that were treated with CAR T-cells. When the documentary was produced, I suggested that it be called ‘Living Drugs’ because that’s the core story of our work.”
Congratulations on being appointed Inaugural Director of the Columbia Initiative in Cell Engineering and Therapy. What do you think the future of CAR T-Cell therapy looks like? Do you have any emerging concerns?
“The proof has been made now. Proof. That’s a strong word. CAR T-cells can save lives and the numbers are growing with each passing year. CAR T-cells could be developed for many other types of cancers, which is what is defining this therapy’s future path. But it’s complicated. You can’t just use exactly the same molecule, the same CAR. With every other possible target, the CAR needs to be changed, adapted, and restructured. Some cancers have additional mechanisms that block the action of any T-cell, including CARs. Those cancers figure out ways to stop the immune system from getting rid of them. Changes are necessary to overcome those barriers, so there’s a lot of activity that will unfold in the years, or even decades, to come. Our T-cells can also be useful for other diseases that are not cancer, which is very exciting. Right now, a category of autoimmune diseases are being treated experimentally with CAR T-cells. There’s a long list of these diseases, but one in particular is Lupus, a very resistant and chronic autoimmune disease. Research focused on using this therapy still has a small number of patients, but it has triggered enormous interest in applying CAR T-cells to a whole range of autoimmune diseases. Severe infections have antibiotics but, sometimes, they can be ineffective. So in that case, you might have to resort to something that’s more complex, like a cell. There can also be problems with transplantation that, if not solved, could at least be helped by engineered T-cells. CAR T-cells were born for cancer, but they are now starting to have a much wider range of applications. My primary concern is that the production of these cells is quite expensive, and if it remains expensive, we won’t be able to give CAR T-cells to everybody who needs them. This challenge is very important to solve — we have to identify better, and less costly ways to produce these cells. If we can make better cells, we will need fewer of them — making them less expensive and more capable of being distributed to a large population of people. The principle of CAR T-cell therapy is out there now. And it created the space for many exciting new types of bioengineering projects in the coming future.”
What advice would you give to readers of The Science Survey and to Bronx Science students interested in research of a similar nature?
“Biology and medicine are fascinating subjects to work on for one’s life. It all starts with education, because the fundamentals are crucial. Biology is like learning a new language. If one studies Japanese, there’s a lot of characters to memorize in the beginning — and then it’s about putting the pieces together. But it only gets more interesting with time, so nobody should lose their enthusiasm. Biology and research is not just about terminology and statistics — there will be a lot of creative and challenging thinking down the road. And the tools are only getting better and more advanced. Whether it’s microscopes or artificial intelligence, there are so many amazing, unimaginable things that will be feasible in the years to come. It’s an exciting direction, but you need those foundations. Once you build that knowledge base, you can find the answers to the questions that no one has been able to answer before. And you can’t be afraid of risks. Whether it’s in medicine, the pharmaceutical industry, research, or even exploring different fields, you need to remember what you are working towards. As part of receiving the Canada Gairdner International Award, I gave lectures to high school students all around Canada. I’m even going to China later today to continue those lectures. It really is rewarding to talk to the youth about the issues that matter. It’s just such a thrilling time to be in the field.”
The influence that Dr. Michel Sadelain has had on cancer treatment goes beyond measure. With this new power of the immune system, he opened a whole new approach toward one of humanity’s biggest medical challenges. His commitment to innovation, access, and patient care has saved countless lives, while creating a future in which cancer will no longer be incurable.
“To me, the doctor provides the medicine of today. And my job is to invent the medicine of tomorrow,” said Dr. Michel Sadelain.