Efficient expression of the tumor-associated antigen MAGE-3 in human dendritic cells, using an avian influenza virus vector

Dendritic cells (DCs) are the most potent inducers of immune reactions. Gen etically modified DCs, which express tumor-associated antigens (TAA), can e fficiently induce antitumor immunity and thus have a high potential as tool s in cancer therapy. The gene delivery is most efficiently achieved by vira l vectors. Here, we explored the capacity of influenza virus vectors to tra nsduce TAA genes. These viruses abortively infect DCs without interfering w ith their antigen-presenting capacity. In contrast to other viruses used fo r DC transduction, influenza viruses can be efficiently controlled by antiv iral pharmaceuticals, lack the ability to integrate into host chromosomes, and fail to establish persistent infections. Genes encoding a melanoma-deri ved TAA (MAGE-3), or the green fluorescence protein (GFP), were introduced into a high-expression avian influenza virus vector. Monocyte-derived matur e DCs infected by these recombinants efficiently produced GFP or MAGE-3. Mo re than 90% of the infected DCs can express a transduced gene. Importantly, these transduced DCs retained their characteristic phenotype and their pot ent allogeneic T cell stimulatory capacity, and were able to stimulate MAGE -3-specific CD8(+) cytotoxic T cells. Thus influenza virus vectors provide a highly efficient gene delivery system in order to transduce human DCs wit h TAA, which consequently stimulate TAA-specific T cells.