Immunotherapy with Dendritic Cells Modified with Tumor-Associated Antigen Gene Demonstrates Enhanced Antitumor Effect Against Lung Cancer

摘要

BACKGROUND: Immunotherapy using dendritic cell (DC) vaccine has the potential to overcome the bottleneck of cancer therapy. METHODS: We engineered Lewis lung cancer cells (LLCs) and bone marrow–derived DCs to express tumor-associated antigen (TAA) ovalbumin (OVA) via lentiviral vector plasmid encoding OVA gene. We then tested the antitumor effect of modified DCs both in vitro and in vivo . RESULTS: The results demonstrated that in vitro modified DCs could dramatically enhance T-cell proliferation ( P .01) and killing of LLCs than control groups ( P .05). Moreover, modified DCs could reduce tumor size and prolong the survival of LLC tumor-bearing mice than control groups ( P .01 and P .01, respectively). Mechanistically, modified DCs demonstrated enhanced homing to T-cell–rich compartments and triggered more naive T cells to become cytotoxic T lymphocytes, which exhibited significant infiltration into the tumors. Interestingly, modified DCs also markedly reduced tumor cells harboring stem cell markers in mice ( P .05), suggesting the potential role on cancer stem-like cells. CONCLUSION: These findings suggested that DCs bioengineered with TAA could enhance antitumor effect and therefore represent a novel anticancer strategy that is worth further exploration.