Selective gene transfer in vitro to tumor cells via recombinant Newcastle disease virus

Cancer Gene Ther. 2005 Mar;12(3):295-303. doi: 10.1038/sj.cgt.7700774.


We developed a novel strategy to target recombinant Newcastle disease virus (NDV) to tumor cells for gene therapy. Modifying the virus with a bispecific fusion protein allowed virus receptor-independent tumor cell binding and gene transfer. The targeting molecule (alpha)HN-IL-2 contains an scFv antibody cloned from a neutralizing hemagglutinin-neuraminidase (HN)-specific hybridoma linked to the human cytokine IL-2. A recombinant NDV expressing the enhanced green fluorescent protein (NDFL-EGFP) was applied to show the expression of foreign genes in virus-infected tumor cells. At 24 hours after infection with the modified virus (NDFL-EGFP/(alpha)HN-IL-2), FACS analysis and fluorescence microscopy revealed neutralization of natural infection in IL-2 receptor-negative Jurkat leukemia cells, but targeted expression of EGFP in IL-2 receptor-positive human leukemia-derived MT-2 cells. The targeted gene delivery of NDFL-EGFP/(alpha)HN-IL-2 in MT-2 cells was blocked by the target ligand human IL-2. Selective virus entry to IL-2 receptor bearing tumor cells was also observed in a mixture of Jurkat and MT-2 cell lines. These results demonstrate that a recombinant NDV carrying a foreign gene can be successfully targeted to a specific tumor through a bispecific protein, which thereby increases the selectivity of gene transfer.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line, Tumor
  • Cricetinae
  • Cricetulus
  • Flow Cytometry
  • Fluoresceins
  • Gene Transfer Techniques*
  • Genetic Therapy / methods*
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use*
  • Green Fluorescent Proteins / metabolism
  • HN Protein / genetics*
  • Humans
  • Interleukin-2 / genetics
  • Microscopy, Fluorescence
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Newcastle disease virus / genetics*
  • Succinimides


  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • Fluoresceins
  • HN Protein
  • Interleukin-2
  • Succinimides
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins