Genetic Engineering Could Make Allo SCTs Safer and More Effective

A new study indicates that certain donor cells in an allogeneic stem cell transplantation could both make the procedure safer and enhance its efficacy.

Stem cell transplantations (SCT) as curative therapy for both leukemia and lymphoma have become increasingly common over the past 20 years. Allogeneic SCTs, in which the patient receives stem cells from a donor, are considered to be riskier chiefly because of the potential for graft-versus-host disease (GVHD).

In other organ transplants, the concern is that the body rejects the organ. In SCTs, the concern is that the organ (or 'graft') will reject the patient. This potentially fatal outcome is known as GVHD. Most of the current strategies to mitigate or suppress GVHD in an allogeneic SCT often limit the transplant's efficacy.

However, a discovery made by Arnab Ghosh and colleagues at Memorial Sloan-Kettering Cancer Center could change that.

TRAIL protein kills bad cells, boosts anti-tumor activity

Researchers discovered that the expression of a specific, cell-death inducing protein known as TRAIL in transplanted donor cells is crucial for an effective anti-tumor response in the recipient. They further discovered that they could engineer immune donor cells to express higher levels of the TRAIL protein, and when they did that, they found those cells were killing the cells that caused GVHD and were also boosting the anti-tumor activity of the graft.

The team has reported its findings in the Journal of Clinical Investigation, concluding, "These data indicate that TRAIL-overexpressing donor T cells could potentially enhance the curative potential of allo-HSCT by increasing GVT response and suppressing GVHD."

Source: JCI