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

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.