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^lowCD11a^high and CD49d^highCD11a^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.

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