Harnessing the immune modulatory effects of IL7 for immunotherapy

Abstract

Immune-based therapies can be broadly divided into strategies aimed toward amplifying beneficial immune responses or attenuating harmful responses, which induce tissue damage to autologous tissues. Interleukin-7 (IL7) holds promise as an immunotherapeutic because of its potent capacity to amplify T-cell based immunity. Its requirement for thymopoiesis and evidence in murine models showing that thymic emigrants are increased when IL7 is administered following bone marrow transplant have led to the hypothesis that IL7 might be able to enhance immune reconstitution following disease and/or therapy induced T-cell depletion. In addition, the IL7 receptor is expressed on most mature CD4+ and CD8+ T-cells and signaling through this receptor can accentuate responses to cognate antigen and induce T-cell activation toward weak antigens. As a result, supraphysiologic levels of IL7 induce widespread peripheral T-cell cycling. Thus, IL7's effects on mature T-cells would be expected to improve overall immune competence in T-cell depleted hosts and may allow IL7 to enhance the therapeutic benefit of antiviral and/or antitumor vaccines.