MRNA-encoded mutant HPV16/18 vaccines promote specific T-cell responses and synergize with anti-PD-1 checkpoint blockade in mediating therapeutic tumor regression in mice.

ABSTRACT:

Background

Persistent infection with high-risk human papillomavirus (HPV) 16 and 18 is a major driver of human cancer, including head and neck and cervical cancers. Although prophylactic vaccines prevent infection, effective therapies for established HPV-related cancers are needed. In this study, we developed a messenger RNA (mRNA)-based therapeutic vaccine encapsulated in lipid nanoparticles (LNP) encoding mutated E6/E7 antigens from HPV16/18 and an optimized co-stimulatory adjuvant (MTS107).

Methods

The mRNA backbone of the vaccine was engineered with mutated HPV16/18 E6/E7 at the N-terminus to prevent the degradation of p53 and pRb. A T2A self-cleaving peptide was incorporated to separate the antigenic components from the co-stimulatory signal genes. An optimal LNP formul

SUBMITTER: Zhang Q 

PROVIDER: S-EPMC12458754 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature