Hiroki Saito1, Satoshi Ando2, Naoya Morishita1, Kyung-Mi Lee3, Dante Dator4, David Dy5, Katsumi Shigemura6, Zainal Adhim7, Ken-Ichi Nibu7, Masato Fujisawa7, Toshiro Shirakawa8. 1. Divison of Translational Research for Biologics, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. 2. Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan. 3. Department of Biochemistry, Korea University College of Medicine, Seoul, Republic of Korea. 4. Department of Urology, National Kidney and Transplantation Institute, Quezon City, Philippines. 5. St. Luke's Medical Center, Global City, Philippines. 6. Division of Urology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 7. Department of Otolaryngology-Head and Neck Surgery, Kobe University Graduate School of Medicine, Kobe, Japan. 8. Divison of Translational Research for Biologics, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe, Japan Department of International Health, Kobe University Graduate School of Health Sciences, Kobe, Japan Division of Urology, Department of Surgery, Kobe University Graduate School of Medicine, Kobe, Japan toshiro@med.kobe-u.ac.jp.
Abstract
BACKGROUND: The antitumor activity of lymphokine activated killer (LAK) cells immunotherapy is not always effective in all patients, especially when used alone. In this study, we investigated the in vitro antitumor activities of a combination of LAK immunotherapy and gene therapy employing an adenovirus carrying the p53 gene (Ad-p53) in human head and neck squamous cell carcinoma. MATERIALS AND METHODS: The in vitro cytotoxicity of LAK cells was tested in H891 cells infected with or without Ad-p53, and the mRNA expression levels of natural killer group 2D ligands (UL16 binding protein (ULBP) 1 to 5) and tumor necrosis factor (TNF-α) in these cells were measured by real-time reverse transcription polymerase chain reaction. RESULTS: Ad-p53 infection increased the cytotoxicity of LAK cells against H891 cells, and also increased the mRNA expression levels of the ULBPs in H891 cells and TNF-α in the LAK cells. CONCLUSION: The antitumor activities of LAK cells in H891 cells were enhanced by Ad-p53. CONCLUSION: The combinational therapy of LAK immunotherapy and Ad-p53 gene therapy may represent a new paradigm for the treatment of head and neck cancer. Copyright
BACKGROUND: The antitumor activity of lymphokine activated killer (LAK) cells immunotherapy is not always effective in all patients, especially when used alone. In this study, we investigated the in vitro antitumor activities of a combination of LAK immunotherapy and gene therapy employing an adenovirus carrying the p53 gene (Ad-p53) in human head and neck squamous cell carcinoma. MATERIALS AND METHODS: The in vitro cytotoxicity of LAK cells was tested in H891 cells infected with or without Ad-p53, and the mRNA expression levels of natural killer group 2D ligands (UL16 binding protein (ULBP) 1 to 5) and tumor necrosis factor (TNF-α) in these cells were measured by real-time reverse transcription polymerase chain reaction. RESULTS: Ad-p53 infection increased the cytotoxicity of LAK cells against H891 cells, and also increased the mRNA expression levels of the ULBPs in H891 cells and TNF-α in the LAK cells. CONCLUSION: The antitumor activities of LAK cells in H891 cells were enhanced by Ad-p53. CONCLUSION: The combinational therapy of LAK immunotherapy and Ad-p53 gene therapy may represent a new paradigm for the treatment of head and neck cancer. Copyright