Journal
TRANSLATIONAL ONCOLOGY
Volume 10, Issue 2, Pages 132-141Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2016.12.002
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Funding
- National Natural Science Foundation of China [81372392]
- key project of Shanghai Municipal Commission of Health and Family Planning [2013zyjb0401]
- Outstanding Yong Doctor Program of Shanghai Municipal Commission of Health and Family Planning [XYQ2013097]
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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.
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