For patients with leukemia, lymphoma, and other blood cancers, a blood or marrow transplant (BMT) can be a potential cure. But when the transplant uses marrow or blood stem cells from a donor, it can have two effects — one harmful and the other helpful.
Now, with a five-year, $2.01 million grant from the National Cancer Institute, Xuefang Cao, MD, PhD, Department of Immunology, is leading research aimed at shutting down the bad side effect and increasing the good one. Both are caused by the donor’s “killer T cells” — white blood cells that are part of the immune system.
Under normal circumstances, T cells are the good guys. Their job is to keep you healthy by finding and destroying foreign cells in your body, such as disease-causing germs. Here’s the problem: when they are transplanted from a donor into a patient, they can get confused about what’s harmful and what’s not, attacking both healthy cells and cancer cells.
- Graft-versus-host disease (GVHD) is the bad side effect. It occurs when the donor’s T cells attack the patient’s normal cells. GVHD affects the skin, liver, and digestive system. While some cases are mild, others can be life-threatening.
- Graft-versus-leukemia (GVL) is the good, desired effect. It occurs when the donor’s T cells recognize cancer cells as foreign and attack them.
Dr. Cao and his colleagues believe that turning off Granzyme B, a molecule present in the donor’s T cells, is the key to alleviating GVHD and increasing GVL. Their theory is that Granzyme B weakens the patient’s antigen-presenting cells (APC), which are part of the immune system and work by training the T cells to kill cancer cells. They also believe Granzyme B attacks the patient’s healthy tissue directly.
If they can prove that theory, the team will take the next step in their research, using a virus to enter the donor’s transplanted cells to deliver “good” genes that can switch off Granzyme B. The success of that effort could mean longer, healthier lives for patients who undergo a blood or marrow transplant.