Molecule in Donor Cells May Be Key to Better Outcomes for Transplant Patients

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.

• 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.

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 side effects are caused by the donor’s “killer T cells” — white blood cells that are part of the immune system.

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 attacks the patient’s healthy tissue and weakens the antigen-presenting cells (APC) that help kill cancer cells. If they can prove this theory, the team will inject a virus into the donor’s transplanted cells to deliver “good” genes that can switch off Granzyme B.

The success of this effort could mean longer, healthier lives for patients who undergo a blood or marrow transplant.