One lesson learned in the last years is that the development of plasmid DNA as cancer vaccine raises key issues such as the need to break immunological tolerance, gradual loss of MHC and antigen in tumour cells, regulatory T cells that could negatively influence the induction of antitumour responses, systemic defects in dendritic cells, secretion of immunosuppressive cytokines, resistance to apoptosis [33, 34] as is discussed elsewhere.