More than six years ago, we started our gene therapy study for patients with glioblastoma, a form of brain cancer. The first patient in our clinical trial was Charlie Burgess.
I’m a medical oncologist, specializing in stem cell and bone marrow transplantation. I’ve always been fascinated by the science behind the bone marrow transplantation, that these stem cells could really engraft long-term and contribute to all the blood cells — red blood cells, platelets and white blood cells, and all the immune cells, for the lifetime of the patient.
I wanted to be a researcher first. I was interested in biochemistry when I was in high school. In Germany, we had a military service, and through my military service, I discovered that I really liked working with people. I learned I’d like to apply the science — biochemistry at that time — to the medical field.
I started medical school at the University of Ulm. Very quickly, I became interested in stem cells. My initial research project was on bone marrow transplantation. At that time, Ulm was one of the few centers in Germany doing bone marrow transplantation, and was very much in touch with Seattle. During rounds, very often I would hear talk about Dr. E. Donnall Thomas and other people from Fred Hutch.
I came [to the U.S.], first, on a bone marrow transplant fellowship with Dr. Karl Blume at Stanford. It was at Stanford that I met Don Thomas and Dr. Rainer Storb. It was through that connection that I came up here [to Seattle]. I then decided to stay and pursue my clinical training in this country and applied for a fellowship at the University of Washington.
When I interviewed [at Fred Hutch], it was an amazing experience meeting all the people I’d heard about. I was very fortunate when I got the call that I could start my fellowship here. That was in 1992.
Dr. Thomas had just retired, but I still saw him almost every day. For the first three years, I worked with Dr. Storb in the lab, really developing stem cell biology and the gene therapy area. I figured, if we understand the stem cell better, we could make more [of them], as we do now for cord blood transplantation.
We could also fix diseases that affect blood stem cells or blood cells. That concept has been very intriguing to me. That has been the center of my research throughout the years.
What we’ve learned, too, is we can actually protect blood stem cells from many of the chemotherapies for cancers that are very toxic to the organs and the blood. At least for certain cancers, we hypothesized that we could potentially protect the stems cells and blood system and then more optimally treat certain cancers with novel chemotherapy.
An 'amazing response' to a gene therapy trial
Charlie Burgess was a psychiatrist from Alaska. He was celebrating — I still remember this story — Fourth of July [in 2009] with his family and friends. Family members noticed he was slurring his speech, becoming a little bit disoriented. Obviously, they became very concerned and took him to the ER, got a CT scan and found a tumor in his brain.
He was rushed to the University of Washington, where he underwent surgery almost right away. They found that he had glioblastoma. Unfortunately, he had the very bad kind of glioblastoma that has the worst prognosis. Ted Kennedy and Beau Biden both had glioblastoma and, unfortunately, died fairly soon after they were diagnosed.
He really wanted to fight this cancer. He had a high-school age daughter, his wife — this wasn’t just a fight for himself, this was really a fight for his family. He reached out to his physician friends and learned about our study. We had many meetings. He decided to participate and become the first patient on our study.
Our study was aimed at very high-risk patients — patients with the worst prognosis. Those are the patients in which the tumor produces a particular protein, which makes the tumor cells resistant to chemotherapy. There is a small molecule called benzylguanine, which can unlock the tumor cell to that chemotherapy, but the problem has been this would [harm] the blood cells.
That’s exactly where the research from my lab came in. We’ve developed ways of engineering the blood stem cells to resist the chemotherapy. In Charlie’s case, we took his blood and marrow stem cells, brought them back to the laboratory, and engineered them. So now, Charlie could get this very powerful chemotherapy.
He responded extremely well. It was very fortunate. He tolerated both the engineering of the stem cells and the chemotherapy. He got nine cycles of this particular chemotherapy, and he survived more than six years after that. That was amazing, and it told us this is something we really need to continue. Most patients with this type of tumor survive about 15 months.
We’ve now treated a total of 10 patients. Eight are now out far enough that we can say all of these patients have survived longer than the 15 months. It is rewarding to be able to help. Most patients I think are very grateful for that.
It’s still very hard [to lose a patient]. Even throughout Charlie’s last months [until his death in October 2015] we stayed very close, and he would call us very often. We are very involved, as physicians. Most patients will ask, “Is this how you would treat your own family member?” I would say, 'Yes, this is what I would do."
Charlie was very grateful. He saw his daughter graduate from college — that was huge for him. That’s what he wanted. This is important for physicians: to do as much as we can to help our patients.