A Memorial Sloan Kettering study suggests that a new, experimental treatment could make bone marrow and stem cell transplantation safer and more effective. Improving the effectiveness of such transplants, while at the same time reducing side effects, is an important goal because it would make such treatments available to a greater number of patients.
A team of experts in the field reported the new findings at the annual meeting of the American Society of Hematology in San Diego this weekend.
The new therapy, which is not yet ready to be evaluated in patients, makes use of immune cells called T cells that are genetically modified to suppress a condition called graft-versus-host disease (GVHD) – a serious complication of transplants in which the donor’s immune system attacks the recipient’s healthy tissues. In addition, the engineered cells help maintain the beneficial graft-versus-tumor (GVT) effect, which enables donor cells to recognize and attack the recipient’s cancer cells.
In the study, mouse models of lymphoma were given genetically engineered T cells following a stem cell transplant from a donor. The T cells were modified to produce high amounts of a protein called TRAIL, which is naturally found in some immune cells in the body and is known to induce programmed cell death (apoptosis) in cancer cells.
The mice that received the engineered T cells had significantly higher survival rates than mice that received normal T cells, which did not overexpress TRAIL. This survival benefit was due to both less tumor growth as well as fewer instances and less-severe instances of GVHD.
The researchers also found that the TRAIL-engineered cells could be used to induce cancer cell death in mouse models of certain renal (kidney) cancers.
The team was led by Arnab Ghosh, a research scholar in the laboratory of Marcel van den Brink, head of Memorial Sloan Kettering’s Division of Hematologic Oncology.
“Our group, along with imaging specialist Vladimir Ponomarev, is currently looking for evidence of similar activities in human T cells that are genetically engineered to overexpress TRAIL,” Dr. Ghosh explains. “We are also studying how TRAIL overexpression in these cells affects the way that a recipient’s immune system reconstitutes itself after a transplant and how these engineered cells can prevent tumor relapse.”