Enhancement of Anti-tumor Activity of Newcastle Disease Virus by the Synergistic Effect of Cytosine Deaminase

Abstract

This study was conducted to investigate enhancement of anti-tumor effects of the lentogenic Newcastledisease virus Clone30 strain (NDV rClone30) expressing cytosine deaminase (CD) gene against tumor cells andin murine groin tumor-bearing models. Cytotoxic effects of the rClone30-CD/5-FC on the HepG2 cell line wereexamined by an MTT method. Anti-tumor activity of rClone30-CD/5-FC was examined in H22 tumor-bearingmice. Compared to the rClone30-CD virus treatment alone, NDV rClone30-CD/5-FC at 0.1 and 1 MOIs exertedsignificant cytotoxic effects (P<0.05) on HepG2 cells. For treatment of H22 tumor-bearing mice, recombinantNDV was injected together with 5-FC given by either intra-tumor injection or tail vein injection. When 5-FCwas administered by intra-tumor injection, survival for the rClone30-CD/5-FC-treated mice was 4/6 for 80 daysperiod vs 1/6 , 0/6 and 0/6 for the mice treated with rClone30-CD, 5-FC and saline alone, respectively. When5-FC was given by tail vein injection, survival for the rClone30-CD/5-FC-treated mice was 3/6 vs 2/6 , 0/6 and0/6 for the mice treated with rClone30-CD, 5-FC or saline alone, respectively. In this study, NDV was used forthe first time to deliver the suicide gene for cancer therapy. Incorporation of the CD gene in the lentogenic NDVgenome together with 5-FC significantly enhances cell death of HepG2 tumor cells in vitro, decreases tumorvolume and increases survival of H22 tumor-bearing mice in vivo.