FasL gene therapy: a new therapeutic modality for head and neck cancer

被引:0
作者
S ElOjeimy
J C McKillop
A M El-Zawahry
D H Holman
X Liu
D A Schwartz
T A Day
J-Y Dong
J S Norris
机构
[1] Medical University of South Carolina,Department of Microbiology and Immunology
[2] Medical University of South Carolina,Department of Otolaryngology – Head & Neck Surgery
来源
Cancer Gene Therapy | 2006年 / 13卷
关键词
adenovirus; gene therapy; Fas ligand; head and neck cancer; apoptosis;
D O I
暂无
中图分类号
学科分类号
摘要
In this study, we investigated the in vitro and in vivo efficacy of Fas ligand (FasL) gene therapy for the treatment of head and neck cancer. Three head and neck squamous cell carcinoma (HNSCC) cell lines (SCC-1, SCC-12, and SCC-14a) were treated with the Fas agonist CH-11, a monoclonal antibody to the Fas receptor, or with a replication-incompetent adenovirus (AdGFPFasL) expressing a modified murine Fas ligand gene fused to green fluorescent protein (GFP). A replication-incompetent adenovirus containing the GFP gene alone was used as a control for viral transduction toxicity (AdGFP). Cell death was quantified using a tetrazolium-based (MTS) assay. Cells were analyzed by flow cytometry to determine the expression of adenoviral and Fas receptors on the surface of the cells. Our results showed that the head and neck cancer cell lines are resistant to cell death induction when treated with the anti-Fas monoclonal antibody CH-11. This resistance can be overcome with AdGFPFasL, which was able to induce cell death in all three cell lines. Apoptosis induction was demonstrated using Western blotting by evaluating poly(ADP-ribose) polymerase, and caspase 9 cleavages. In addition, intratumoral injections of AdGFPFasL into SCC-14a xenografts induced significant growth suppression of tumors, indicating that FasL gene therapy may provide a new efficient therapeutic modality for HNSCC that is worthy of a clinical trial.
引用
收藏
页码:739 / 745
页数:6
相关论文
共 99 条
[1]  
Ferris RL(2004)Progress in head and neck cancer immunotherapy: can tolerance and immune suppression be reversed? ORL 66 332-340
[2]  
Carvalho AL(2005)Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database Int J Cancer 114 806-816
[3]  
Nishimoto IN(2004)The present and future for gene and viral therapy of directly accessible prostate and squamous cell cancers of the head and neck Future Med 1 1-9
[4]  
Califano JA(1994)Purification and characterization of the Fas-ligand that induces apoptosis J Exp Med 3 873-879
[5]  
Kowalski LP(1994)Human Fas ligand: gene structure, chromosomal location and species specificity Int Immunol 10 1567-1574
[6]  
Norris JS(1993)Molecular cloning and expression of the Fas ligand, a novel member of the tumor necrosis factor family Cell 6 1169-1178
[7]  
Norris KL(1997)Membrane Fas ligand kills human peripheral blood T lymphocytes, and soluble Fas ligand blocks the killing J Exp Med 12 2045-2050
[8]  
Holman DH(1995)FAS-induced apoptosis is mediated via a ceramideinitiated RAS signaling pathway Immunity 4 341-351
[9]  
El-Zawahry A(1999)Treatment of experimental glioma by administration of adenoviral vectors expressing Fas ligand Hum Gene Ther 10 1641-1648
[10]  
Keane TE(1999)Adenovirus-mediated expression of Fas ligand induces apoptosis of human prostate cancer cells Cell Death Differ 6 175-182