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p16INK4A adenovirus-mediated gene therapy for human head and neck squamous cell cancer

J W Rocco1, D Li, W H Liggett

  • 1Department of Otolaryngology and Head and Neck Surgery, Head and Neck Cancer Research Division, Johns Hopkins University, Baltimore, Maryland 21203-6402, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|July 24, 1998
PubMed

Insights

Gene therapy using Ad5-p16 effectively inhibits head and neck squamous cell cancer (HNSCC) growth. This study shows Ad5-p16 halts cancer cell cycle progression and reduces tumors in vivo, offering a promising HNSCC treatment.

Area of Science:

  • Oncology
  • Gene Therapy
  • Molecular Biology

Background:

  • Inactivation of the p16INK4A tumor suppressor gene is a frequent event in head and neck squamous cell cancer (HNSCC).
  • Restoring p16INK4A function presents a potential therapeutic strategy for HNSCC.

Purpose of the Study:

  • To develop and evaluate a recombinant adenovirus (Ad5-p16) for delivering the p16INK4A gene.
  • To assess the efficacy of Ad5-p16 in inhibiting HNSCC cell growth and tumor progression in vitro and in vivo.

Main Methods:

  • Construction of a replication-defective adenovirus vector expressing p16INK4A (Ad5-p16).
  • In vitro studies using human HNSCC cell lines to assess cell growth inhibition and cell cycle arrest (flow cytometry).
  • In vivo studies in a nude mouse model with established HNSCC tumors to evaluate Ad5-p16 treatment effects.

Main Results:

  • Ad5-p16 treatment significantly inhibited HNSCC cell growth in vitro (up to 96% efficiency).
  • Ad5-p16 induced a G1-S cell cycle arrest in up to 90% of treated cells.
  • In vivo, Ad5-p16 significantly reduced or stabilized established HNSCC tumors in mice compared to controls (P < 0.008).

Conclusions:

  • Ad5-p16 demonstrates significant antitumor activity against human HNSCC in vitro and in vivo.
  • Ad5-p16 holds potential for treating various stages of head and neck cancer, including advanced, unresectable, metastatic, or residual disease.

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