Development and characterization of recombinant adenoviruses encoding human p53 for gene therapy of cancer

Hum Gene Ther. 1994 Sep;5(9):1079-88. doi: 10.1089/hum.1994.5.9-1079.


We have constructed recombinant human adenoviruses that express wild-type human p53 under the control of either the Ad 2 major late promoter (MLP) or the human cytomegalovirus (CMV) immediate early gene promoter. Each construct replaces the Ad 5 E1a and E1b coding sequences necessary for viral replication with the p53 cDNA and MLP or CMV promoter. These p53/Ad recombinants are able to express p53 protein in a dose-dependent manner in infected human cancer cells. Tumor suppressor activity of the expressed p53 protein was assayed by several methods. [3H]Thymidine incorporation assays showed that the recombinant adenoviruses were capable of inhibiting DNA synthesis in a p53-specific, dose-dependent fashion. Ex vivo treatment of Saos-2 tumor cells, followed by injection of the treated cells into nude mice, led to complete tumor suppression using the MLP/p53 recombinant. Following a single injection of CMV/p53 recombinant adenovirus into the peritumoral space surrounding an in vivo established tumor derived from a human small cell lung carcinoma cell line (NIH-H69), we were able to detect p53 mRNA in the tumors at 2 and 7 days post-injection. Continued treatment of established H69 tumors with MLP/p53 recombinant led to reduced tumor growth and increased survival time compared to control treated animals. These results indicate that recombinant adenoviruses expressing wild-type p53 may be useful vectors for gene therapy of human cancer.

MeSH terms

  • Adenoviruses, Human / genetics*
  • Animals
  • Base Sequence
  • Carcinoma, Small Cell / pathology
  • Carcinoma, Small Cell / therapy*
  • Cytomegalovirus / genetics
  • DNA Replication
  • DNA, Complementary / genetics
  • DNA, Recombinant / genetics
  • DNA, Viral / genetics
  • Defective Viruses / genetics*
  • Female
  • Genes, p53*
  • Genetic Therapy*
  • Genetic Vectors*
  • Humans
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Sequence Data
  • Neoplasm Transplantation
  • Neoplasms / genetics
  • Neoplasms / therapy*
  • Promoter Regions, Genetic
  • Recombinant Fusion Proteins
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / deficiency
  • Tumor Suppressor Protein p53 / genetics


  • DNA, Complementary
  • DNA, Recombinant
  • DNA, Viral
  • Recombinant Fusion Proteins
  • Tumor Suppressor Protein p53