The day that Dr. Hootie Warren's future fell into place is etched in his mind. A Harvard Medical School student at the time, he was perusing the Boston Globe on October 8, 1990, when he came upon an article about Dr. E. Donnall Thomas' Nobel Prize win that day for pioneering bone marrow transplantation—and suddenly, Warren felt his siren call.
"I read about the development of bone marrow transplantation and decided that day I wanted to come to Seattle," Warren said. "Putting someone's immune system inside someone else's body is an incredibly profound thing. It's mind-boggling. And it's the clearest example of successful immunotherapy we have in medicine."
Warren spent most of his early career at the Hutchinson Center studying the curative way newly transplanted immune-system cells, called T-cells, attack leukemia cells. It's called the graft-vs.-leukemia effect and doesn't happen for all patients. So, in hopes of improving transplant outcomes, Warren set out to learn how the successful donor cells recognize a patient's leukemia.
His focus led to an important discovery: He was able to isolate the T-cells that zero in on leukemia cells. By expanding them in the lab and giving them back to the patient, Warren took advantage of the tremendous specifity of the immune system to target the patient's leukemia without harming normal tissue. This technique, know as adoptive T-cell therapy, lessens a sometime serious side effect of transplantation called graft-vs.-host disease in which the transplanted immune-system cells see the patient's cells as foreign.
"I'm very interested in trying to figure out when cancer responds, why is it doing that? When immunotherapies work, by and large, we have no clue what's going on there," Warren said. "If we could only understand what's happening in those individuals and extract the principles, then perhaps we could understand why it's not working in the majority of people. We could either tailor the therapy or perhaps combine it with other approaches so more people benefit."
Currently, Warren is working to develop T-cell therapy for kidney and colon cancer. His team hopes to treat other solid-tumor cancers as well, if they can identify the receptors on such cells and target them. They are particularly seeking targets among a group of genes identified in many solid tumors and blood cancers, but not found in most normal cells. Because these genes are linked with cancer, researchers like Warren are hopeful they can be targeted precisely without causing collateral damage to healthy tissues.
While Warren's laboratory efforts get most of his focus, about 20 percent of his time is spent with patients through the Seattle Cancer Care Alliance, where he sees current patients and long-term survivors.
"I'm very lucky. I have not just one, but two great jobs," he said. "I really love doing science and I love taking care of patients.
"There are a lot of scientists who work hard just because they love science, but I think the ability to understand the human dimension of cancer very much gives meaning to what I'm doing in the lab. Taking care of transplant patients is motivating because when transplants work, they’re just miraculous. When they don't work—which is all too often—you see the reason to work hard and keep working. The two endeavors feed off each other."