Genetically engineered Newcastle disease virus expressing human interferon-1 induces apoptosis in gastric adenocarcinoma cells and modulates the Th1/Th2 immune response

Interferon-1 (IFN-1), a recently discovered cytokine of the type III IFN family, was found to be a therapeutic alternative to type I IFN in terms of tumors. Using reverse genetics technique, we generated a recombinant Newcastle disease virus (NDV) LaSota strains named as human IFN-1 recombinant adenovirus (rL-hIFN-1) containing human IFN-1 gene and further evaluated the expressing of IFN-1 in human gastric adenocarcinoma cell line SGC-7901 after infected with rL-hIFN-1 by using western blot analysis, RT-PCR and immunofluorescence analyses. IFN-l specific receptor IFNLR1 was detected on several gastric tumor cell lines including SGC-7901 and AGS and on PBMCs. The expression of the IFN-1 proteins reached a high level detected in the supernatant harvested 24 h after the infection of tumor cells. The proliferation changes of SGC infected with rL-hIFN-1 was significantly inhibited compared with NDV-infected group. Apoptosis was significantly induced by rL-hIFN-1 in gastric cancer cells compared with NDV virus tested by TUNEL assay, western blot analysis and Annexin V flow cytometry. Due to the high dose of IFN-1 expressed by the rL-hIFN-1-infected tumor cells, the immune study showed that rL-hIFN-1 increased IFN- production [the T helper cell subtype 1 (Th1) response] and inhibited interleukin (IL)-13 production [the T helper cell subtype 2 (Th2) response] to change the Th1/Th2 response of tumor microenvironment which inhibited tumor growth. This study aims at building recombinant NDV rL-hIFN-1 as an efficient antitumor agent.