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Cancer Biol Med. 2019 May;16(2):288-298. 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.

Author information

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.

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 CD8αlowCD11ahigh and CD49dhighCD11ahigh 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

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