The Antitumour Efficacy Of A Novel Oncolytic Adenovirus Ad-TD-RFP For Human Nasopharyngeal Carcinoma

BackgroundNasopharyngeal carcinoma （NPC） is a common cancer in China. Eighty percent cases of NPC occurred in China, especially in Guangdong, Guangxi, Fujian, Jiangxi and Hunan provinces. Radiotherapy is the main method to treat nasopharyngeal carcinoma. The five-year survival of the early nasopharyngeal carcinoma patients treated by radiotherapy reaches90%-95%. But, due to the biological characteristics of NPC:occult, strong invasion, and fast lymph node metastasis, more than70%of the newly diagnosed cases were in stage III or IV, which resulted in a low five-year survival of20%～30%^[1,2]Therefore, there is an urgent need to find out a new strategy for tumor therapy. The therapy should have a better selectivity for the tumor cells and more specific mechanism. Moreover, it won’t have the antagonism to the existing conventional treatments. Replication-selective oncolytic adenoviruses （RSOA） is a novel anticancer treatment^[3].This oncolytic adenoviruses can selectively kill cells and replicate in tumor cells but not in normal cells. The first generation of oncolytic adenovirus with a deletion of E1B55k gene, dl1520^[4], similar virus in China named H101, has been widely used to head and neck cancer therapy as the world’s first oncolytic virus by State Food and Drug Administration in2005^[5] dl1520has been used for local advanced primary tumours in pancreatic cancer patients. dl1520therapy was well tolerated, but the therapeutic efficacy was very limited. Based on our previous findings, we created a new generation of oncolytic adenovirus, named Ad-TD-RFP, in which there were triple deletions of E1ACR2, E1B19k and E3gp19k and retention of the E1B-55k and E3B genes.ObjectiveAssessment of the antitumour efficacy of dl1520and Ad-TD-RFP in vitro and in C666-1subcutaneous xenograft model in nude mice.MethodsThe cytotoxicity of the novel oncolytic adenovirus Ad-TD-RFP and control virus,dl1520to nasopharyngeal carcinoma cell line, C666-1cells, was determined by MTS（3-（4,5-dimethylthiazol-2-yl）-5-（3-carboxymethoxyphenyl）-2-（4-sulphophenyl）-2H-tetrazolium） assay; viral replication of Ad-TD-RFP and dl1520were detected by TCID50assay （Tissue culture infective dose50%）. C666-1cells were implanted subcutaneously into one flank of BALB/C nude mice. The xenografts were injected intratumorally with Ad-TD-RFP and dl1520through four different directions.ResultsThe EC50value of Ad-TD-RFP and dl1520were （107.6±3.2） pt/cell and （174.1±4.0） pt/cell,（P<0.001）. TCID50results showed that the novel oncolytic adenovirus Ad-TD-RFP replication in C666-1cell was significantly more than dl1520at different time points（24h、48h、72h、96h）,（P<0.001）. The tumor growth was significantly regressed in Ad-TD-RFP-treated nude mice compared to dl1520-treated nude mice （P<0.05）.ConclusionThe antitumour efficacy of the novel oncolytic adenovirus Ad-TD-RFP for nasopharyngeal carcinoma cell line（C666-1） is more efficacious than dl1520in vitro and in vivo. This study suggests that the novel oncolytic adenovirus Ad-TD-RFP may be an effective agent for treatment of human nasopharyngeal carcinoma.