Combination radiation and adenovirus-mediated P16(INK4A) 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.
Rhee
Juong G
JG
Department of Radiation Oncology, University of Maryland School of Medicine, BRB 6013, 655 West Baltimore Street, Baltimore, MD 21201, USA. jrhee@umaryland.edu
Li
DaQing
D
O'Malley
Bert W
BW
Suntharalingam
Mohan
M
D000256:Adenoviridae; D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D002453:Cell Cycle; D045744:Cell Line, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D018014:Gene Transfer Techniques; D019942:Genes, p16; D015316:Genetic Therapy / Q000379:methods*; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D018714:Radiotherapy, Adjuvant; D011881:Radiotherapy, Computer-Assisted
D019941:Cyclin-Dependent Kinase Inhibitor p16