Combination Radiation and Adenovirus-Mediated p16INK4A Gene Therapy in a Murine Model for Head and Neck Cancer

Since adenoviral P16(INK4A) gene transfer has shown limited promise in preclinical studies, we developed a strategy combining ionizing radiation (x-rays) with Ad-P16 gene therapy. Both radiation (2 Gy) and Ad-P16 alone demonstrated anti-tumor responses. The combination of radiation and Ad-P16 in vitro showed an augmented therapeutic response. Two head and neck squamous cell carcinoma (HNSCC) cell lines treated with Ad-P16 demonstrated positive staining to annexin V and terminal deoxynucleotidyl-transferase, suggesting apoptosis. When the HNSCC cell lines were grown in nude mice, the anti-tumor response by Ad-P16, radiation, and combination therapy ranged from limited benefit of the single-agent therapy to a statistically significant additive response to combination therapy. Our data suggest that Ad-P16 gene therapy may prove effective in treating human HNSCC that is refractory to radiation therapy.