Attenuated plasmodium sporozoite expressing MAGE-A3 induces antigen-specific CD8+ T cell response against lung cancer in mice

Dong Zhou; Hong Zheng; Quanxing Liu; Xiao Lu; Xufeng Deng; Li Jiang; Bing Hou; Yong Fu; Feng Zhu; Yan Ding; Wenyue Xu; Jigang Dai

doi:10.20892/j.issn.2095-3941.2018.0309

Attenuated plasmodium sporozoite expressing MAGE-A3 induces antigen-specific CD8+ T cell response against lung cancer in mice

Cancer Biol Med. 2019 May;16(2):288-298. doi: 10.20892/j.issn.2095-3941.2018.0309.

Authors

Dong Zhou¹, Hong Zheng¹, Quanxing Liu¹, Xiao Lu¹, Xufeng Deng^{1

2}, Li Jiang¹, Bing Hou¹, Yong Fu³, Feng Zhu³, Yan Ding³, Wenyue Xu³, Jigang Dai¹

Affiliations

¹ Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
² Department of Cardiothoracic Surgery, The First People's Hospital of Zunyi, Zunyi 563000, China.
³ Department of Pathogenic Biology, Third Military Medical University, Chongqing 400037, China.

PMID: 31516749
PMCID: PMC6713645
DOI: 10.20892/j.issn.2095-3941.2018.0309

Abstract

Objective: Cancer vaccines that rely on tumor antigen-specific CD8⁺ T cell responses, are promising anti-cancer adjuvant immunotherapies. This study investigated whether genetically attenuated Plasmodium sporozoite (GAS) could be used as a novel vector to induce antigen-specific CD8⁺ T cell responses against lung cancer.

Methods: We constructed GAS/MAGE-A3, a recombinant GAS engineered to express the lung cancer-specific antigen, melanoma-associated antigen 3 (MAGE-A3), and assessed its therapeutic effects against lung cancer.

Results: Robust parasite-specific CD8α^lowCD11a^high and CD49d^highCD11a^high CD4⁺ T cell responses as well as a MAGE-A3-specific CD8⁺ T cell response were induced in GAS/MAGE-A3-immunized mice. Adoptive transfer of GAS/MAGE-A3-induced CD8⁺ T cells from HLA-A2 transgenic mice into lung cancer-bearing nude mice inhibited tumor growth and prolonged survival.

Conclusions: These findings demonstrate that GAS/MAGE-A3 induces a strong MAGE-A3-specific CD8⁺ T cell response against lung cancer in vivo, and indicate that GAS is a novel and efficacious antigen delivery vector for antitumor immunotherapy.

Keywords: MAGE-A3; Vaccine; genetically attenuated sporozoites; lung cancer; malaria.