Synergy Effects of HPV E6-E7 Encoding mRNA and Nucleic Acid Immunostimulators Improve Therapeutic Potential in TC-1 Graft Tumor.

Cervical cancer is the second most common cancer among women globally and the most prevalent cancer in developing countries, which was caused by human papillomavirus (HPV) infection. Messenger RNA (mRNA) vaccines have opened up new avenues for vaccine development and pandemic preparedness with potent scalability, which may possess the potential antitumor effects of an mRNA-HPV therapeutic vaccine containing nononcogenic E6 and E7 proteins. Here, we reported a lipid nanoparticle (LNP) plus nucleic acid immunostimulators (CPG 1018 and Poly I:C) mRNA vaccine platform. The LNP-CPG 1018 capsulated HPV E6-E7 mRNA significantly promoted the maturation of bone marrow-derived dendritic cells (BMDC) in vitro and were capable of efficiently migrating to lymph nodes (LN) in vivo. In TC-1 tumor-bearing mice, the subcutaneous immunization of LNP-CPG 1018 capsulated HPV E6-E7 mRNA elicited robust tumor-specific T-cell immunity, reshaped the tumor microenvironment, and inhibited tumor growth. In conclusion, the LNP-CPG 1018 system is a promising delivery platform for facilitating the development of HPV E6-E7 mRNA cancer vaccines.