Imagine if we could treat deadly diseases by generating healthier versions of the very building blocks of our bodies—blood stem cells. That's the vision of Dr. Hans-Peter Kiem, whose Hutch laboratory is working to make such therapies a reality.
"Not long ago, this was science fiction," said Kiem, who holds the Stephanus Family Endowed Chair for Cell and Gene Therapy.
Kiem's cutting-edge research reflects his longstanding interest in blood stem cell transplantation, now one of the standard treatments for many blood cancers, in which the patient receives an infusion of blood stem cells, either from a donor or from the patient's own multiplied cells. The idea is that the new stem cells will grow into disease-free blood cells — a concept that Kiem's research takes a step further.
"Stem cells can do everything," said Kiem, who first came to the Hutch as a fellow in 1992 and joined the faculty five years later. "If we can correct defective stem cells, we can cure diseases."
Kiem and his colleagues investigate how stem cells can be extracted from sick patients, manipulated at a genetic level and then delivered back to them to treat a range of diseases, from infections like HIV to genetic diseases to aggressive cancers.
One ongoing research effort confronts a major challenge in cancer treatment: Patients can receive only so much chemotherapy at a time, or else their blood cell counts may drop to a level that invites infections, anemia, excessive bleeding and other serious health complications. In such a scenario, the patient must stop receiving chemotherapy until the cell counts recover to healthy levels — but meanwhile, the cancer can worsen.
Kiem's lab has developed a way to extract a patient's blood stem cells and insert a special "resistance" gene that is designed to protect the cells from damage by common chemotherapy drugs such as temozolomide and BCNU. An infusion of these enhanced cells could give new hope to patients with the most aggressive form of brain cancer — glioblastoma — which is very difficult to treat. A small study for glioblastoma patients that Kiem started in fall 2009 is showing promising initial results and continuing to expand.
Kiem is also planning a study of patients with AIDS and lymphoma, who would receive blood stem cells with two inserted genes: one that counteracts the HIV infection and one that protects the patient from chemotherapy’s effects.
More recently Kiem has extended his work to derive blood stem cells from a new class of stem cells called induced pluripotent stem cells. What makes pluripotent stem cells promising for new treatments is that they can be derived from readily accessible adult tissues, such as skin cells, and can mature into many other types of tissues and cells, including blood stem cells. These blood stem cells could in turn be expanded and used for blood stem cell transplantations, offering a new treatment option for patients with defective marrow or immune function.