Authors: M.L. Figueiredo, M. Figueiredo Neto, J.W. Salameh, R.E. Decker, R. Letteri, D. Chan-Seng, T. Emrick
Summary: We have examined the role of a novel targeted cytokine, interleukin-27 (IL-27), modified at the Cterminus with a dual targeting and therapeutic heptapeptide, in treating prostate cancer. IL-27 has shown promise in halting tumor growth and mediating tumor regression in several cancer models, including prostate cancer. We describe our findings on the effects of targeted IL-27 gene delivery on prostate cancer cells in vitro and in vivo and how the targeting enhances bioactivity of the IL-27 cytokine. We applied the IL-27 gene delivery protocol utilizing sonoporation (sonodelivery) with the goal of reducing prostate tumor growth in an immunocompetent TC2R C57/BL6 model. The reduction in tumor growth and effector cellular profiles implicate targeted IL-27 as more effective than an untargeted version of IL-27 in promoting bioactivity, as assessed by STAT1 and IFNγ reporter genes. Moreover, enhanced antitumor effects and significantly higher accumulation of NKT and CD8 effector cells in the tumors were observed. These results support a novel IL-27-based targeting strategy that is promising since it shows improved therapeutic efficacy while utilizing simple and effective sonodelivery methods.
Source: Molecular Therapy - Methods & Clinical Development, 2020