Therapeutic effect of targeted Fas-expressing adenoviruses method combining [gamma][delta] T cells in a mouse model of human ovarian carcinoma

• Published in: Oncology letters Vol. 15; no. 2; p. 2555
• Main Authors: Zeng, Dingyuan, Lin, Jiajing, He, Hongying, Tan, Guangping, Lan, Ying, Jiang, Fuyan, Sheng, Shuting
• Format: Journal Article
• Language: English
• Published: Spandidos Publications 01.02.2018
• Subjects: Adenoviruses; Care and treatment; Development and progression; Gene expression; Genetic aspects; Health aspects; Oncogenes; Ovarian cancer
• ISSN: 1792-1074
• DOI: 10.3892/ol.2017.7599

The present study aimed to investigate the therapeutic effect and safety of targeted use of Fas-expressing adenoviruses combined with [gamma][delta] T cell-mediated killing to treat human ovarian cancer xenografts in BALB/c mice. Shuttle plasmids containing control elements of human telomerase reverse transcriptase promoter and two-step transcriptional amplification system were constructed and packaged into adenovirus-5 vectors to generate expression of an exogenous Fas gene. A mouse xenograft model of human ovarian carcinoma was constructed. A total of 35 BALB/c mice were randomly divided into five groups, which were injected with PBS, [gamma][delta] T cells, Fas-expressing adenoviruses, taxol, or Fas-expressing adenovirus and [gamma][delta] T cells. The weight and volume of tumors in mice in each group was monitored. Tissue sections of the various tissues of mice in the Fas-expressing adenovirus and [gamma][delta] T cells group was compared with those in the PBS group to evaluate the safety of Fas-expressing adenovirus and [gamma][delta] T cells in the treatment of human ovarian cancer xenograft tumors. The results of the present study indicated that mice in all treatment groups were alive at the end of the treatment course. Tumor weight and volume was the highest in the PBS group, followed successively by the adenovirus group, the [gamma][delta] T cell group, the adenovirus and [gamma][delta] T cell group, and the taxol group. The weight and volume inhibition rate in adenovirus and [gamma][delta] T cell group were significantly higher compared with in the PBS group (P<0.05). Pathological observation of tissue samples revealed that none of vital organs in the adenovirus and [gamma][delta] T cell group developed any evident morphological changes during treatment, when compared with healthy controls. In conclusion, the combined therapy with Fas-expressing adenoviruses and [gamma][delta] T cells is efficient and safe for the treatment of mouse human ovarian carcinoma xenografts. Key words: gene therapy, tumor specific promoter, two-step transcriptional amplification system, Fas gene, ovarian cancer xenograft