Objective:Cancer vaccines that rely on tumor antigen-specific CD8+ T cell responses, are promising anti-cancer adjuvant immunotherapies. This study investigated whether genetically attenuatedPlasmodium 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 cancerin vivo, and indicate that GAS is a novel and efficacious antigen delivery vector for antitumor immunotherapy.