Inhibition of carcinoma cell growth and metastasis by a vesicular stomatitis virus G-pseudotyped retrovector expressing type I insulin-like growth factor receptor antisense

A replication-defective, vesicular stomatitis virus G-pseudotyped, Moloney murine leukemia virus retroviral vector (vLTR-IGF-IRAS) was generated in wh ich a type I insulin-like growth factor receptor (IGF-IR) antisense fragmen t is expressed in a bicistronic mRNA with an enhanced green fluorescent pro tein (EGFP) reporter under the control of a potent long terminal repeat (LT R). The suitability of these retroparticles for gene therapy was tested wit h highly metastatic, carcinoma H-59 cells, which depend on IGF-IR expressio n for tumorigenicity and metastasis. Transduction with these, but not with control retroviral particles expressing EGFP only, resulted in a 70% reduct ion in IGF-IR levels and the loss of IGF-IR-regulated functions. Moreover, the ability of vLTR-IGF-IRAS retroparticle-transduced tumor cells to form e xperimental hepatic metastases was significantly reduced relative to contro ls. The results identify retrovector-mediated delivery of IGF-IR antisense as a potential strategy for cancer gene therapy.