Immunotherapy with Dendritic Cells Modified with Tumor-Associated Antigen Gene Demonstrates Enhanced Antitumor Effect Against Lung Cancer |
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Authors: | Tao Jiang Xiao Chen Wei Zhou Guoxin Fan Peilin Zhao Shengxiang Ren Caicun Zhou Jun Zhang |
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Institution: | 2. Department of Anthropotomy and Histo-Embryology, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China;3. Department of Spinal Surgery, Shanghai Tenth People''s Hospital, Tongji University School of Medicine, 301 Middle Yan Chang Road, Shanghai 200433, China;4. Division of Hematology, Oncology and Blood & Marrow Transplantation, Department of Internal Medicine, Holden Comprehensive Cancer Center, University of Iowa Carver College of Medicine, Iowa City, Iowa |
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Abstract: | 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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Keywords: | Address all correspondence to: Peilin Zhao PhD Department of Anthropotomy and Histo-Embryology Tongji University School of Medicine 1239 Siping Road Shanghai 200092 PR China or Shengxiang Ren MD PhD and Caicun Zhou MD PhD Department of Medical Oncology Shanghai Pulmonary Hospital Thoracic Cancer Institute Tongji University School of Medicine No 507 Zheng Min Road Shanghai 200433 P R China |
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