Delivery of interferons and siRNA targeting STAT3 using lentiviral vectors suppresses the growth of murine melanoma

Interferons (IFNs) have been investigated as important cytokines in immunotherapy. The use of IFNs in cancer immunotherapy has had limited success. In this study, IFN genes were delivered into B16 melanoma cells by lentiviral vectors, and their effects on B16 melanoma were comprehensively analyzed. Type II IFN significantly impaired the viability of B16 cells in vitro. Expression of IFN alpha and IFN beta in B16 cells efficiently suppressed the establishment of inoculated melanoma. However, intratumoral delivery of IFNs alone with lentiviral vectors had no therapeutic effects on established melanoma. To address the lack of response, a lentivector was constructed to simultaneously transfer therapeutic genes and small interfering RNAs (siRNAs). IFNs and siRNA targeting signal transducer and activator of transcription 3 (STAT3), which is a major immune suppressive transcription factor in melanoma, were delivered simultaneously into the tumor milieu. This treatment successfully rescued the response to IFN gamma and attenuated the growth of established tumors. This method has the potential to improve the therapeutic effects of IFNs in cancer immunotherapy.