Oncolytic virus changes tumor environment to improve HPV-positive tumor vaccine targeting HPV16 proteins

mRNA-ubiquitin (UB)-E6/E7 vaccination significantly enhanced immune responses and antitumor activity in HPV-positive tumors.

• The mRNA-UB-E6/E7 construct improved antigen-specific immune responses compared to current HPV E6/E7 vaccines.
• Increased cytotoxic T lymphocyte (CTL) activity and higher frequencies of E7-specific CD8⁺ T cells were observed with mRNA-UB-E6/E7.
• Monotherapy with mRNA-UB-E6/E7 showed enhanced antitumor activity, although tumor control was not complete.
• Combination therapy with the oncolytic herpes simplex virus (FusOn-H2) resulted in improved therapeutic efficacy.
• This improvement was linked to increased intratumoral CD8⁺ T cell infiltration and enhanced CTL activity and IFN-γ production.
• Effective tumor vaccination may require robust systemic T cell responses alongside efficient T cell function within the tumor microenvironment.

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