Enhanced Antitumor Response Mediated by the Codelivery of Paclitaxel and Adenoviral Vector Expressing IL-12

Abstract

It has been well-established that chemo-immunotherapy using cytotoxic drugs and appropriate cytokines offers a promising approach for the treatment of neoplastic diseases. In view of this, to improve melanoma treatment effect, our study developed a new codelivery system (AL/Ad5/PTX) that paclitaxel (PTX) and adenovirus encoding for murine interleukin-12 (Ad5-mIL-12) were incorporated into anionic liposomes (AL). First, AL/Ad5/PTX complexes were prepared by incorporating Ad5 into anionic PTX liposomes using calcium-induced phase change. Second, the size distribution and zeta potential of AL/Ad5/PTX were investigated. Third, the results of in vitro transduction assays showed that PTX introduced into AL/Ad-luc or AL/Ad5-mIL-12 highly enhanced gene transduction efficiency in B16 cells than naked Ad5 or AL/Ad complexes while it had no comparability in A549 cells. Finally, a melanoma-bearing mouse model was established to assess the antitumor effect. Tumor growth inhibition and prolonged survival time, accompanied by increased mIL-12 or interferon-γ (IFN-γ) expression levels in serum or tumor sites, were observed in mice treated with AL/Ad5-mIL-12/PTX, as compared with those treated with either AL/Ad5-mIL-12 or AL/PTX. In conclusion, these results suggested that codelivery of Ad5-mIL-12 and PTX incorporated into AL could be a relatively efficient strategy for the treatment of melanoma.