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Transl Oncol. 2017 Apr;10(2):132-141. doi: 10.1016/j.tranon.2016.12.002. Epub 2017 Jan 25.

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

Author information

1
Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507 Zheng Min Road, Shanghai, 200433, China.
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
Department of Anthropotomy and Histo-Embryology, Tongji University School of Medicine, 1239 Siping Road, Shanghai 200092, China. Electronic address: plzhao@yahoo.com.
5
Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507 Zheng Min Road, Shanghai, 200433, China. Electronic address: harry_ren@126.com.
6
Department of Medical Oncology, Shanghai Pulmonary Hospital, Thoracic Cancer Institute, Tongji University School of Medicine, No. 507 Zheng Min Road, Shanghai, 200433, China. Electronic address: caicunzhou_dr@163.com.
7
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.

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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