Cancer patients who receive a stem cell transplant as part of their treatment undergo a temporary depletion of certain white blood cells known as T cells, which are critical to the proper functioning of the immune system. Until they can regenerate a sufficient number of T cells, these patients are at serious risk of infection by pathogens such as viruses, bacteria, and fungi — as well as of having their cancer return.
Now Memorial Sloan Kettering researchers have shown for the first time that administering a growth factor called interleukin-7 (IL-7) can help patients regenerate T cells more quickly after transplantation. The pharmaceutical version of IL-7, called CYT107, was developed by Cytheris, a clinical-stage biopharmaceutical company. Although the study involved only 12 people, it raises hopes for development of a therapy that would allow patients to regain full immune function faster and improve their chances of survival.
“IL-7 may be the T cell growth factor we’ve been looking for,” says physician-scientist Marcel R. M. van den Brink, head of Memorial Sloan Kettering’s Division of Hematologic Oncology and a member of the Sloan Kettering Institute’s Immunology Program. He led the research along with physician-scientist Miguel-Angel Perales, who conducted the phase I clinical trial, and they reported the results in the December 6 issue of the journal Blood.
Improving T Cell Recovery
Dr. van den Brink specializes in treating cancers and blood disorders using allogeneic stem cell transplantation, in which patients receive blood-forming stem cells from a donor to replace their own malfunctioning blood cells. In previous research in mice, Dr. van den Brink and colleagues had demonstrated that IL-7, a naturally occurring protein that carries signals between cells, could enhance the development and survival of T cells when given following allogeneic transplants.
Despite the promise shown by IL-7 in the laboratory, there was concern that boosting T cell recovery after a transplant could cause a complication known as graft-versus-host disease (GVHD), in which donor T cells attack the recipient. Risk of GVHD depends on the number of T cells present in the transplanted cells, with higher numbers of T cells bringing greater risk. Because of this threat, the researchers tested the IL-7 therapy in transplant patients receiving stem cells from which most of the T cells had been removed — an approach known as T cell depletion.
In the trial, 12 Memorial Sloan Kettering patients with blood cancers (acute myelogenous leukemia, myelodysplastic syndrome, or chronic myelogenous leukemia) who had received allogeneic transplants received injections of escalating doses of CYT107 once a week for three consecutive weeks. The trial was conducted mainly to demonstrate that the treatment was safe, although the researchers also looked for any evidence that IL-7 was having an effect on the transplanted T cells.
“To our surprise we already noticed increases in T lymphocyte counts even after the lowest dose of IL-7, which was not expected to have much effect,” says Dr. Perales.
The treatment did not appear to have any toxic effects, and only one patient experienced GVHD.
In addition, subsequent analysis of each patient’s blood and lymph fluid showed that certain subsets of T cells had increased in number significantly — especially in a group known as effector memory T cells. These T cells fight off repeat infections and prevent a person from catching the same illness more than once.
The results suggest IL-7 holds promise as a treatment to help patients recover immune function after an allogeneic stem cell transplant.
“Although it’s a small trial, any therapy that shows a beneficial effect in people is a significant advance,” Dr. van den Brink says. “However, larger studies are needed to confirm the safety and success of this approach before it becomes part of a standard treatment for patients receiving an allogeneic transplant.”