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Studies Investigate New Methodologies to Improve Recovery and Survival Strategies for Patients Undergoing Hematopoietic Cell Transplantation
Date:12/10/2011

ffect. Recognizing this challenge, researchers sought to create a new method to suppress GVHD without compromising the GVT effect by using genetically engineered donor T-cells that over-express a protein known to induce cell death in an effort to specifically attack cancer cells.

The protein, Tumor Necrosis Factor (TNF)-Related Apoptosis-Inducing Ligand, or TRAIL, is naturally expressed on some immune cells in the body. TRAIL targets tumor cells and keeps them from multiplying and spreading by interacting with death receptor molecules, which are highly expressed on the surface of tumor cells, making them more susceptible to therapeutic targeting using TRAIL.

To evaluate the effect of genetically engineered donor T-cells over-expressing TRAIL (TRAIL+) on GVHD and GVT, investigators from Memorial Sloan-Kettering Cancer Center performed HCT using TRAIL+ donor T-cells versus control donor T-cells in experimental mouse models with cancerous tumors. Mice that received TRAIL+ donor T-cells displayed significantly higher survival rates, indicating greater antitumor activity than in those treated with control donor T-cells. The researchers also used donor TRAIL+ progenitor T-cell with autologous (stem cells from the patient) HCT in tumor-bearing mice and found a significantly higher anti-tumor effect compared with controls. In addition to enhanced GVT effect, the transplant recipients treated with TRAIL+ T-cells experienced significantly less severe GVHD. Researchers further found that the immune cells, which trigger GVHD, also express TRAIL-sensitive death receptors, and TRAIL+ T-cells can suppress GVHD by targeting these cells.

"Our data show that donor T-cells over-expressing TRAIL can suppress GVHD while simultaneously enhancing the GVT effects. We hope this approach will provide fresh insights into separating cancer cell killing from indiscriminate killing of normal tissues," said Arnab Ghosh, MD, PhD, lead author and a Research Scholar in the lab
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SOURCE American Society of Hematology
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