[Oncolytic adenovirus expressing CCL19 enhances immunity against gastric cancer in mice]

Objective To explore whether oncolytic adenovirus expressing CCL19 can inhibit the growth of gastric cancer cells and activate anti-tumor immune response. Methods Mouse CCL19 gene was inserted into the E3 region of oncolytic adenovirus Ad5 to obtain engineered oncolytic adenovirus Ad5-CCL19. The expression of CCL19 in Ad5-CCL19-infected mouse MFC cells was detected by Western blotting. The effects of Ad5-CCL19 on the proliferation of MFC cells, MGC803 cells and BGC823 cells were tested by MTT assay. The anti-tumor activity of Ad5-CCL19 in vivo was examined by MFC cell subcutaneous transplantation tumor model. Immunofluorescence histochemical staining was used to detect CD4 and CD8 expression in tumor tissue. The secretion levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in tumor infiltrating T cells were detected by flow cytometry. Results Ad5-CCL19 could effectively infect MFC cells to secrete CCL19. Also, Ad5-CCL19 could induce significant dose-dependent cytotoxicity against target cells in vitro. The experiment in vivo showed that Ad5-CCL19 had stronger inhibitory effects on MFC cell tumor than Ad5 in the mice, and it could effectively enhance the infiltration of CD4⁺ T cells and CD8⁺ T cells and increase the secretion of IFN-γ and TNF-α in tumor tissues. Conclusion Ad5-CCL19 can significantly infect MFC gastric cancer cells to inhibit their growth and improve the anti-tumor immune activity of the tumor site.