Disclosed are methods and compositions for gene therapy for tumors. Cytotoxic agents are selectively expressed in endothelial cells of tumor blood vessels, and delivered to tumor cells adjacent to the blood vessels, producing a bystander effect such that all the cells in contact with the transfected cells are killed or permanently growth arrested. In particular, cytotoxic gene products secreted from the transfected cell using a secretory signal sequence, include a membrane permeability domain at the N- or C-terminus that can shuttle the cytotoxic domain into non-transfected cells and back into transfected cells.