IL-7 in allogeneic transplant: clinical promise and potential pitfalls

Much progress has been made in the field of allogeneic stem cell transplantation. However, one major barrier is the delay in immune recovery that can persist for months post-transplant and results in increased susceptibility to infection and relapse of malignancy. Strategies to improve immune recovery must be balanced with the potential for those therapies to exacerbate graft vs host disease. Interleukin 7 is a member of the gammac cytokine family that is required for T-cell development and maintenance of naïve T-cell populations. In addition, IL-7 plays a major role in the expansion of mature T-cells that occurs during lymphopenia and therapeutic IL-7 can enhance both quantitative and functional immune recovery following T-cell depletion. Thus, this agent holds much promise as an immunorestorative agent and as an adjuvant to vaccines or adoptive immunotherapy. Clinic trials with IL-7 are underway. Murine studies with IL-7 in the allogeneic transplant have demonstrated that the potent immune effects of this agent can also be achieved in this setting. However, these studies have indicated that the potential for IL-7 to worsen GVHD exists and that this effect may abrogate the immune benefits. Thus, careful consideration of how best to incorporate IL-7 into allogeneic trials will be needed if the full potential of this agent is to be realized.