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

表达 MAGE-A3 的减毒疟原虫子孢子诱导小鼠抗肺癌抗原特异性 CD8+ T 细胞反应

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

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.

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.

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.

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.

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