Gene therapy for hepatocellular carcinoma using adenoviral vectors delivering a gene encoding IL-17A-neutralizing antibody fragments.

: High interleukin 17A (IL17A) expression in hepatocellular carcinoma (HCC) tissue promotes HCC development. This study is explore a method to inhibit HCC growth by neutralizing IL17A in the HCC microenvironment. A novel type 5 adenoviral vector (Ad5) that carries DNA sequences encoding specific neutralizing IL17A recombinant antibody fragments was developed in this research. After locally injected into tumor tissues, the Ad5 transduced into tumor cells. This leading to the expression of the anti-IL17A recombinant antibody fragments in the HCC tissue and consequently to an inhibition of HCC growth by neutralizing IL17A. The stability of the antibody fragments was optimized by different structures design. Stable HCC cell lines that secrete IL17A continuously were constructed and showed stronger invasion and migration ability than control HCC cell lines. Additionally, the enhanced migration and invasion ability was partially reversed by applying the adenoviral vectors. These results suggest that IL17A might promote HCC growth by enhancing the invasion and migration ability of hepatoma cells. The antibody fragments from Ad5 neutralized IL17A locally in turn inhibited the growth of HCC tumors. In conclusion, the local administration of Ad5 vectors encoding IL17A-neutralizing antibody fragments provides a new option for HCC immunotherapy.