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

Tao Jiang; Xiao Chen; Wei Zhou; Guoxin Fan; Peilin Zhao; Shengxiang Ren; Caicun Zhou; Jun Zhang

doi:10.1016/j.tranon.2016.12.002

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

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

Authors

Tao Jiang¹, Xiao Chen², Wei Zhou², Guoxin Fan³, Peilin Zhao⁴, Shengxiang Ren⁵, Caicun Zhou⁶, Jun Zhang⁷

Affiliations

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: [email protected].
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: [email protected].
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: [email protected].
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.