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

作者：Dong Zhou, Hong Zheng, Liu Quanxing, Xiao Lu, Deng Xufeng, Jiang Li, Bing Hou, Yong Fu, Feng Zhu, Yan Ding, Wenyue Xu, Dai Jigang · 发表于：Cancer Biology and Medicine · 年份：2019 · DOI：10.20892/j.issn.2095-3941.2018.0309 · 被引用次数：24 · 研究领域：Immunotherapy and Immune Responses、Immune Cell Function and Interaction、CAR-T cell therapy research

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 low CD11a high and CD49d high CD11a 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.