A local gene therapy scheme for the delivery of
type I interferons could be an alternative for the treatment of
melanoma. We evaluated the cytotoxic effects of
interferon-β (IFNβ) gene lipofection on tumor cell lines derived from three human cutaneous and four canine mucosal
melanomas. The cytotoxicity of human IFNβ gene lipofection resulted higher or equivalent to that of the corresponding addition of the
recombinant protein (rhIFNβ) to human cells. IFNβ gene lipofection was not cytotoxic for only one canine
melanoma cell line. When cultured as monolayers, three human and three canine IFNβ-lipofected
melanoma cell lines displayed a remarkable bystander effect. As spheroids, the same six cell lines were sensitive to IFNβ gene transfer, two displaying a significant multicell resistance phenotype. The effects of conditioned IFNβ-lipofected canine
melanoma cell
culture media suggested the release of at least one soluble thermolabile cytotoxic factor that could not be detected in human
melanoma cells. By using a secretion signal-free truncated human IFNβ, we showed that its intracellular expression was enough to induce cytotoxicity in two human
melanoma cell lines. The lower cytoplasmatic levels of
reactive oxygen species detected after intracellular IFNβ expression could be related to the resistance displayed by one human
melanoma cell line. As IFNβ gene transfer was effective against most of the assayed
melanomas in a way not limited by relatively low lipofection efficiencies, the clinical potential of this approach is strongly supported.