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.