Delivery of interleukin-22 binding protein (IL-22BP) gene by cationic micelle for colon cancer gene therapy

Abstract

Gene therapy has provided an alternative strategy for cancer therapy. As an important cytokine, interleukin-22 (IL-22) is not only critical in reinforcing innate immune defenses and tissue regeneration, but also involved in the initial establishment of tumors. A soluble-secreted receptor of the cytokine IL-22, IL-22 binding protein (IL-22BP), binds IL-22 and prevents its binding to the functional transmembrane receptor IL-22R1 complex, inhibiting IL-22-based intracellular cancer proliferation signal. In this work, a novel IL-22BP-based cancer gene therapy strategy was reported for the first time. It was established by delivering IL-22BP gene with a newly developed non-viral gene vector DMP. The DMP cationic micelles were prepared by modifying monomethoxy poly(ethylene glycol)-poly(ϵ-caprolactone) with DOTAP lipid through self-assembling. The anti-cancer efficacy of the DMP/IL-22BP complex was studied on a colon cancer model by intraperitoneal administration. Our results demonstrated that the secretory expressed IL-22BP cytokine effectively inhibited cancer growth both in vitro and in vivo. Multiple anti-cancer mechanisms including IL-22 blocking, apoptosis inducing, lymphocyte infiltration and angiogenesis inhibition were indicated to be involved while no pathology changes were observed in healthy tissues. These results suggest the DMP/IL-22BP complex to be a potential candidate for cancer gene therapy.