Combination of oncolytic adenovirus ZD55 harboring TRAIL-IETD-MnSOD and cytokine-induced killer cells against lung cancer.

Abstract

BackgroundOur study aimed to investigate the effect of cancer-targeting gene-virotherapy and cytokine-induced killer (CIK) cell immunotherapy on lung cancer.MethodsCIK cells were obtained from peripheral blood mononuclear cells using interferon (IFN)-γ, interleukin (IL)-2, and CD3 monoclonal antibody. The CIK cells were infected with oncolytic adenovirus ZD55 harboring tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), manganese-containing superoxide dismutase (MnSOD), and TRAIL-isoleucine-aspartate-threonine-glutamate (IETD)-MnSOD. The cells were then cocultured with lung cancer cell lines A549 and NCI-H1650, normal cell line BEAS-2B, or injected into an A549 xenograft mouse model.ResultsProliferation, colony formation, and invasion of A549 and NCI-H1650 cells were significantly inhibited by co-cultivation with CIK cells carrying oncolytic adenoviruses (in order) ZD55-TRAIL-IETD-MnSOD > ZD55-TRAIL + ZD55-MnSOD > ZD55-MnSOD > ZD55-TRAIL. Compared to BEAS-2B cells, the production of IFN-γ, TNF-α, and lactate dehydrogenase (LDH) in tumor cells was increased. Tumor volume in the xenograft model and Ki-67 expression in tumor samples were reduced after injection of CIK cells carrying oncolytic adenoviruses, in the same order as the in vivo experiments. Levels of IFN-γ, TNF-α, and LDH contents were also increased in the same order.ConclusionsOur studies confirmed the high efficacy of combined oncolytic adenovirus ZD55 harboring TRAIL-IETD-MnSOD and CIK cells against lung cancer.