A cancer stem cell vaccine engineered to express Interleukin-15 and its receptor induces T cell proliferation

Introduction. Interleukin-15 (IL-15), a member of the 4-α-helix bundle family of cytokines is a powerful activator and inducer of maturation of both NK and CD8+ cytolytic T cells. It also activates and expands CD8+ T memory cell populations without stimulating immunosuppressive CD4+CD25+ T-regulatory cells. This suggests that IL-15 may be useful as an immunotherapy for the treatment of cancer. In a phase I clinical trial, infusions of recombinant human IL-15 achieved tumor regressions; however, treatment was associated with a systemic inflammatory response syndrome.† In an effort to enhance antitumor activity and reduce systemic side effects, we studied an approach using a vaccine enriched for cancer stem cells (CSCs) genetically altered to express murine (m) IL-15 and its receptor (mIL-15Ralpha).