Centenary Institute develops new therapeutic approach to prevent GVHD in blood cancer patients

Sydney’s Centenary Institute has developed a new therapeutic approach that could help to improve outcomes for patients undertaking treatment for blood cancer.

Haematopoietic stem cell transplantation (bone marrow transplant) is a treatment used for blood cancers such as leukemia and lymphoma. Immune cells derived from the donor stem cell graft help to keep the cancer at bay, improving long-term prognosis. However, a serious complication associated with this treatment is graft-versus-host disease (GVHD) in which donor cells attack normal host tissues such as the skin, bowel and liver.

GVHD is estimated to affect between 30-60% of patients who undergo this treatment, with a mortality rate of approximately 50%. Thus, a major challenge associated with stem cell transplants is how to best reconstitute the patient with the donor immune cells they need to fight off tumour recurrence and infection, while at the same time preventing development of GVHD.

The Centenary Institute has used animal models to understand why the unwanted immune responses responsible for GVHD occur, and how they can be prevented.

Head of the Centenary Institute’s T Cell Biology Program, Professor Barbara Fazekas de St Groth, said this study focused on regulatory T cells, which are involved in regulating a wide variety of immune responses.

“We discovered that regulatory T cells are highly effective in preventing GVHD, but only when they are present in high numbers before any GVHD-causing cells are transplanted,” she said.

“In order to achieve this, we developed new ways to help donor regulatory T cells to survive and proliferate in the transplanted animals. We showed that regulatory T cells function to dampen the stimulatory capacity of the dendritic cells that drive immune responses. When there are too few regulatory T cells, dendritic cells are able to trigger spontaneous immune cell activation, leading to GVHD.”

The Centenary Institute’s findings indicate that new therapies designed to achieve high numbers of regulatory T cells before introduction of other donor immune cells will be of major benefit to patients undergoing stem cell transplantation. Professor Fazekas de St Groth also discovered the gold standard technology used internationally for purifying human regulatory T cells for patient therapy, and will use this in future trials of regulatory T cell therapy to prevent GVHD in patients undergoing treatment for blood cancer.