IL-27 is an anti-inflammatory
cytokine that has been shown to have potent anti-
tumor activity. We recently reported that systemic delivery of
IL-27 using recombinant adeno-associated virus (rAAV) induced depletion of Tregs and significantly enhanced the efficacy of
cancer immunotherapy in a variety of mouse
tumor models. A potential caveat of systemic delivery of
IL-27 using rAAV is that there is no practical method to terminate
IL-27 production when its biological activity is no longer needed. Therefore, in this work, we tested if directly injecting AAV-IL-27 into
tumors could lead to similar anti-
tumor effect yet avoiding uncontrolled
IL-27 production. We found that high levels of
IL-27 was produced in
tumors and released to peripheral blood after AAV-IL-27 intra-tumoral injection. AAV-IL-27 local
therapy showed potent anti-
tumor activity in mice bearing
plasmacytoma J558
tumors and modest anti-
tumor activity in mice bearing B16.F10
tumors. Intra-tumoral injection of AAV-IL-27 induced infiltration of immune effectors including CD8+ T cells and NK cells into
tumors, caused systemic reduction of Tregs and stimulated protective immunity. Mechanistically, we found that
IL-27 induced T cell expression of CXCR3 in an IL-27R-dependent manner. Additionally, we found that AAV-IL-27 local
therapy had significant synergy with anti-PD-1 or T cell adoptive transfer
therapy. Importantly, in mice whose
tumors were completely rejected,
IL-27 serum levels were significantly reduced or diminished. Thus, intra-tumoral injection of AAV-IL-27 is a feasible approach that can be used alone and in combination with anti-PD-1 antibody or T cell adoptive transfer for the treatment of
cancer.