Physician-scientist Marcel van den Brink is Co-Director of the Parker Institute for Cancer Immunotherapy (PICI) at Memorial Sloan Kettering. PICI, which includes MSK and five other founding partner institutions, is geared toward unlocking the power of the immune system to fight cancer. Dr. van den Brink also heads the Division of Hematologic Oncology at MSK and holds the Alan N. Houghton Chair in immunology.
We spoke with him recently about his work and his role in PICI.
How does being a part of the Parker Institute for Cancer Immunotherapy provide a boost to your research?
Among the many advantages of PICI, one is that it will allow us to focus on extensive immune monitoring — collecting and studying samples from patients who are undergoing treatments with different kinds of immunotherapy. This process will enable us to learn how patients’ bodies respond to treatments and suggest ways we can make immunotherapies more effective, with fewer side effects.
The samples include not only blood and tumors but also stool. This connects to an important project in my own lab, on the role of the microbiota in immune responses. The microbiota is the community of microorganisms in the human body. Some are helpful and some are harmful.
For several years, my lab has been studying how cancer treatments can affect the balance of microbes in the body, which influences how well a patient fares. We’ve worked in close collaboration with MSK’s Lucille Castori Center under the direction of my friend and colleague Eric Pamer.
In particular, our first studies have looked at the role of the microbiota in graft-versus-host disease, a potentially fatal condition in which immune cells from donated bone marrow attack the cancer patient’s healthy tissues. We’ve also studied how the microbiota affect graft-versus-tumor activity, in which the donor’s cells attack the patient’s cancer, as well as cancer relapse.
How will PICI funding benefit MSK and the field of immunotherapy overall?
As a field, immunotherapy is in a special situation. For many years, the idea of using the immune system to fight cancer was considered to be a dead end. Researchers on both the lab and clinical sides were discouraged from focusing on it.
Now the field has broken open with all these recent successes — such as immunotherapy cancer drugs and treatments with engineered immune cells — and everyone is looking for scientists with an interest in immunotherapy for cancer. But there aren’t many, because they haven’t been trained.
PICI will provide the means to encourage and train smart young talent. It will do this through its emphasis on fellowships, scholarships, and pilot grants that fund very early-stage research, as well as generous start-up packages for young faculty.
What areas of immunotherapy research are you most excited about?
Going all the way back to the beginning, MSK has been a pioneer in immunotherapy. In all the areas that are most important now — bone marrow transplantation, checkpoint blockade drugs, and cell therapies — we are founders and leaders.
I’m excited to see how those treatments will advance, but I’m even more excited to learn what the next frontier will be. There are many things we still don’t know about the immune system. The next big area could be natural killer cells, which several MSK researchers are studying. It also could be the role of the microbiota, as I mentioned before, or activation of the thymus, which is another important focus of my lab.
Could you talk about that research?
The thymus is a small organ that sits just above your heart and makes T cells, an important component of the immune system. T cells are essential to every cancer immunotherapy that’s available now. As we age, our thymuses shrink and lose their ability to generate new cells. This makes it harder for patients’ immune systems to recover after chemotherapy and other treatments.
Some immunotherapies involve harnessing T cells so they can recognize and attack cancer. But if patients don’t have many T cells, these therapies don’t work as well as they could. If we can find ways to boost the activity of the thymus to make more T cells — and especially a broader range of types of T cells — that would help many people.
This research has implications beyond cancer. For example, flu vaccines frequently don’t work in the elderly because older people can’t make the T cells needed to mount the immune response that allows the vaccine to work.
Tell us about the path you took to get to where you are today.
I grew up in a city called Leiden, in the Netherlands near the Hague, and went to medical school there. I was always interested in doing research in addition to being a doctor. When I graduated there were a lot of new findings about immune cells, so I decided to focus my research efforts in that area.
My interest in cancer came from a patient I met as a medical student. It was my first time working overnight on the hospital ward, and I cared for a 24-year-old patient — about the same age as me — who was dying of metastatic melanoma. After that experience, I was motivated to find better ways to treat patients like him.
I eventually settled on bone marrow transplantation. In a bone marrow transplant, or BMT, chemotherapy and radiation kill the cancer in the patient’s blood and bone marrow. Then new marrow is given to help healthy blood cells grow back. I focus on allogeneic transplants, in which marrow from a donor is used, as opposed to marrow that’s taken from the patient.
We know that an important component of the effectiveness of BMT comes when the donor T cells attack the patient’s remaining cancer. This makes allogeneic bone marrow transplantation a cancer immunotherapy.
Then you came to MSK to further your BMT research?
Yes. I was hired by Richard O’Reilly, who is truly a giant in the field of bone marrow transplantation. He did some of the early, critical studies on transplants from unrelated donors, going back to the 1970s. It was a major plus that I would have a chance to work with him.
I came at a time when MSK was making huge investments in research. In the decade from 2000 to 2010, we doubled the number of researchers in our labs. I could see month by month and year by year how our research depth and strength were growing. Now we’re reaping the benefits of that investment. Immunotherapy is just one of those gains.
One thing I always mention to people who are thinking about working here is the interest that the basic scientists have in taking their science into the clinic. They want to work with clinical samples and find the clinical relevance in their discoveries.
That connection is made possible by all of the institutional support our scientists are given, as well as the examples set by our top scientists. I find it fascinating that we’re all ultimately focused on the cancer problem in one way or another and want our research to benefit our patients.