Abstract: Vascular endothelial growth factor/vascular permeability factor (VEGF/VPF) is one of the most frequently expressed angiogenic factors in tumors. Development of VEGF antagonists has become an important approach in cancer therapy. Here we describe a novel anti-VEGF strategy by preventing VEGF secretion in tumors cells. We utilize the fact that placenta growth factor-1 (PIGF-1), a member of the VEGF family lacking detectable angiogenic activity, preferentially forms intracellular heterodimers with VEGF in cells co-expressing both factors. We constructed a retroviral vector containing human PIGF-1 or VEGF with a C-terminal KDEL sequence, which is a signal for endoplasmic reticulum (ER)-retention in mammalian cells. Transduction of murine Lewis lung carcinoma (LLC) cells with the retro-PIGF-1-KDEL construct almost completely abrogates tumor growth and induces tumor dormancy.