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In this article:
Kelly Paulson, M.D., Ph.D., will lead a visionary initiative at Swedish dedicated to harnessing the power of the body’s own immune system to treat (and defeat) cancer.
We will gain a better understanding of why certain treatments work and why others don’t.
Dr. Paulson’s work will help refine immunotherapies to make them more targeted, and ultimately more successful, in the elimination of cancer cells.
Kelly Paulson, M.D., Ph.D., is a medical oncologist and researcher with a passion for advancing immunotherapy in the fight against skin cancer and other solid tumors. She is an author or co-author on more than 45 scientific papers, the majority focused on understanding the interplay between the immune system and skin cancers (Merkel cell carcinoma and melanoma) and exploiting anti-tumor immunity for cancer monitoring and detection, prognostication and treatment.
For our series on the leadership team behind the Paul G. Allen Research Center at Swedish Cancer Institute, we spoke with Dr. Paulson from her family’s Seattle-area home, which was buzzing with the energy of her two active young children. During a wide-ranging discussion, Dr. Paulson shared her vision for the Center for Immuno-oncology (CIO), insight into the workings of immunotherapeutic cancer treatment and her hopes for advancing the ways we diagnose, understand and, ultimately, treat cancer.
From your perspective as a physician and researcher, tell us a little bit about the mission and foundational tenets of the Paul G. Allen Research Center at Swedish Cancer Institute.
The Paul G. Allen Research Center at Swedish Cancer Institute is an opportunity to build on Swedish's strong tradition of research. Mr. Allen’s transformative gift is intended to support deep research dives into some of the most pressing questions in cancer research related to improving prevention, understanding and treatment of patients with cancer. These form the three pillars that are associated with the center.
Dr. Chuck Drescher will lead a pillar called the Initiative for Cancer Prevention and Early Detection (IPED), which is focused on improving and developing new methods for the early detection of cancer. How can we find cancer at its very earliest phases? And whether that's new blood biomarkers or new genomics testing or new imaging modalities, how do we find cancer when it's still in its earliest, most curable stage?
The pillar led by Dr. Hank Kaplan is the Initiative for Molecular and Genomic Evaluation of Cancer (IMGEC). IMGEC’s goal is to deeply understand how we can target cancer at a molecular level. What makes each patient's cancer tick? And can we identify weaknesses in that particular cancer to most effectively target our treatments against that type of cancer?
IMGEC’s first major project will focus on breast cancer because it affects so many [people] here in Washington state and nationally and internationally. Dr. Kaplan is leading his center and his initiative to expand on this infrastructure from there and extend these wonderful, leading-edge, genomic technologies to other cancer disease spaces.
I’m the interim lead of the third pillar, which is the Center for Immuno-oncology (CIO). We're really focused on how to fight cancer. The newest cancer treatments out there are immune therapies, which empower your own body to fight cancer. It's actually the body's natural way of fighting off cancer. But how can we exploit the immune system to fight cancers? And the reason we're so excited about using the immune system to fight cancers is the potential for a long-lasting, durable, permanent response.
We've seen in diseases like melanoma and certain lymphomas and certain leukemias that the immune system and immune therapy have taken previously incurable cancer and made them, in some cases, curable even at stage four metastatic disease. And we really want to understand why immunotherapy works when it works and how we can extend those successes to diseases where immunotherapy doesn't yet achieve those outcomes.
For the layperson, could you give us a brief explanation of immunotherapy and its applications in treating cancer?
Our immune system consists of several parts. It's the way that the body fights off things foreign to our systems. These include things like bacteria and viruses and cells with mutations, like cancer cells, where a cell’s normal DNA has been damaged. That can be through UV light, as in the case of a melanoma, or through tobacco smoke, as in the case of lung cancer.
We all have many, many damaged cells circulating throughout our bodies, and the body normally does a good job getting rid of them. Unfortunately, cancer cells, in some cases, have learned to hide from the immune system, so we have different kinds of immune therapies that help to make cancer more visible to the immune system.
These include therapies like monoclonal antibodies, which we have heard a lot about during COVID-19; one type targets cell surface proteins, which are on the outside of cancer cells. We have [drugs] that make these cancer cells visible to the body and prevent the cell from hiding. We also have monoclonal antibody therapies that target immune checkpoint inhibitors. These don't bind to the cancer directly; they help rejuvenate the immune system, make it less tired and, in general, amplify and charge it up. That extra energy boost basically reverses immune exhaustion. The immune system then is empowered to be able to overcome a lump of cancer that was otherwise tiring the immune system out, both by its size and through the cancer cells telling the immune system to go to sleep and to get old through synapses.
So, immunotherapy basically reverses one of the tricks that cancer uses to get around. And again, we can get these very nice immune responses that are long-lasting. Immunotherapy also includes things like stem cell transplants, and then the new version of stem cell transplant, which involves CAR T-cells. With this therapy, we take different types of immune cells out of the body, and we give them something that helps the immune cells to directly seek cancer cells and destroy them. Essentially, we genetically engineer the immune cells as a sort of mini-transplant to go back in the patient, and basically now we tell the immune system not only to see bad things, but we tell it what specifically to seek, attack and destroy.
How does the work of the CIO fit into what’s going on in the larger world of cancer treatment and research?
Swedish has a strong tradition and strong history of excellent care and treatment for patients with cancer. We also have a strong, active cancer research program. I was just reading information about scientific research on Twitter, and there were over 20 publications from Swedish investigators in just the last two months, which is pretty incredible. And we also have something like 40 active principal investigators (senior academics, scientists or physicians who prepare, conduct and oversee scientific research), so the efforts of the Swedish Cancer Institute are truly incredible.
Mr. Allen’s gift will let us dive deeper into our immunotherapy trials and not just treat patients, but to help understand why these treatments work, how they work and do the right studies to say, "How can we extend these successes to more people and more reliably?"
Your work initially focused on skin cancer, specifically Merkel cell carcinoma. Will you take that work into your role at the center?
Yes, absolutely. I've been working on Merkel cell cancer and actually skin oncology for a long time, so I also have an interest in melanoma and am involved in quite a few melanoma studies. We do have leading-edge Merkel cell carcinoma immunotherapy research trials open here at Swedish. And so, I absolutely still see Merkel cell cancer patients as part of my day-to-day care.
We are also building a comprehensive skin oncology program because these diseases are something that both affect a lot of people in Washington state, and actually, the nation. Melanoma, Merkel cell carcinoma and other aggressive skin cancers are dramatically increasing in terms of the number of people that they're affecting. They're diseases that we know we can do things for, so we have these immune therapies now, not only in the metastatic setting, but actually in stage two, stage three, so aggressive, local-regional disease now, to help reduce the chance of this coming back and becoming a dangerous cancer. And we know that these are both an area where we can be successful and, at the same time, where more research is needed.
About half the patients that receive immunotherapy for melanoma and for other skin cancers, like Merkel cell carcinoma, benefit from those immune therapies. That means that half of them don't. We know we can change that. Merkel cell is also really important in helping us understand why immunotherapy works sometimes and not others. In my role as a doctor, I meet a patient with melanoma and then I meet a patient with Merkel cell carcinoma, and I can't tell them whether immunotherapy is going to work for them or not. I have to try it and see. So, understanding why this treatment works, when it does and how it does will hopefully help us to make these treatments better for the next generation of patients.
How do you believe Mr. Allen’s gift reflects his ideas?
I didn't have the opportunity to know Paul personally. But I do know that he was very invested in using technology to make the world better, which is what we want to do as well. And we also want to expand our understanding about what drives cancer, such as what makes a cancer cell cancerous. We also want to deepen our understanding of really complicated things like the immune system. And we want to do this in a digital, integrated way that brings investigators together.
This is very important because big advances in cancer are not happening from one person in a corner anymore; they're happening with large groups of people who look at cancer in different ways, with different tools and technologies. These groups are working together to ask how we can understand the problem and then work together to solve it. And so I think Paul’s vision of using technology to bring people together so that they could work together to make the world a better place is well-reflected in the center, our three complementary institutes and our goal of working as a team to understand cancer.
Courtesy Allen Institute/Paul G. Allen Frontiers Group
Why is Swedish the right home for the center?
Research is really important in terms of what we do, and Swedish has a really strong history of research and continues to be very supportive of research. We also have a very strong history of genomic investigations.
Another thing that's just really fantastic about Swedish is our staff. I have to give a shout-out to our nurses, especially. I think we have the best nurses in the world. And it's fantastic to do clinical care and research at a place where not only are the doctors great, but the nurses and the rest of the staff as well. It's a place where patients receive truly compassionate care from every caregiver.
What do you want people to know about the center and the work of the CIO in particular?
All of the investigators within the CIO truly believe that the immune system is the way to cure cancer. We remain hopeful and optimistic that we are going to be able to use the immune system to cure more and more cancers, seeing the progress that we've seen in some disease spaces. We've seen in disease spaces that have so far really not had a lot of hope in the advanced settings. So, it's our hope for the future that by understanding how to better engage the immune system in the fight against cancer, we will help more patients with cancer to fight, but to ultimately win that fight.
How you can help
Research at this scale requires a significant investment in technology, personnel and laboratory resources. Your philanthropic support will unlock the secrets of cancer’s evolution and how patients respond to treatments by building a team of experts in research and data collection. Learn more and give today at www.swedishfoundation.org/PaulGAllenResearchCenter.
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