Gene Therapy for Bladder Cancer Using Adenoviral Vector

Mol Urol. Summer 2001;5(2):47-52. doi: 10.1089/109153601300177547.

Abstract

Background and purpose: Bladder cancer is common. Current treatment for patients with superficial bladder cancer involves transurethral resection followed by adjuvant bacillus Calmette-Guérin (BCG) administration. Adjuvant BCG has been reported to be effective in 38% to 68% of patients; however, more than 30% of patients do not respond. Because p53 mutations are common among superficial bladder cancers, we tested the feasibility of using p53 as a gene therapy agent for targeting superficial tumors, which are easily accessible using an intravesical approach.

Materials and methods: Wild-type p53 was transduced into various human and murine bladder cancer cell lines (HTB9, KU-1, and MBT-2) using a recombinant adenoviral vector (Ad5CMV-p53) in vitro. Also, subcutaneous tumors were established and then treated with intratumoral injection of Ad5CMV-p53 or control viruses.

Results: In vitro assays revealed significant growth suppression of target cells by Ad5CMV-p53 in comparison with those receiving the control Ad5-CMV-PA vector or untreated control cells. In vivo studies using subcutaneous bladder tumor models established in syngeneic mice demonstrated that the rate of tumor growth and volume was reduced to a greater extent by 14 days of intratumoral injection of Ad5CMV-p53 rather than Ad5CMV-PA. Furthermore, the survival of host animals bearing tumors that were infected with Ad5CMV-p53 was significantly longer than that of the control group treated with Ad5CMV-PA (P < 0.01).

Conclusion: Our data suggest that Ad5CMV-p53 is effective in suppressing bladder cancer growth and improving host survival.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Apoptosis / physiology
  • Carcinoma / therapy
  • Cell Division
  • Genes, p53*
  • Genetic Therapy / methods*
  • Genetic Vectors*
  • Humans
  • Mice
  • Survival Rate
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / therapy*