ImmunologyMar 12, 2024

Preventing and Treating HPV-Related Cancer with an mRNA Vaccine That Targets Immune Cells

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 18, 2026

Abstract

The mRNA vaccine tHA-mE7-mE6 resulted in complete tumor regression in an E6 and E7 tumor model.

The vaccine is designed to eliminate tumorigenicity by introducing mutations into HPV E6 and E7.
A truncated influenza protein was fused with the vaccine to enhance antigen uptake by immune cells.
Treatment with tHA-mE7-mE6 (mRNA) induced a stronger therapeutic response compared to mE7-mE6 (mRNA).
The therapy led to a robust CD8 T-cell immune response, which is associated with tumor prevention and cure.
Increased infiltration of dendritic and natural killer cells in tumors was observed following treatment.

Simplified

Persistent human papillomavirus (HPV) infection is associated with multiple malignancies. Developing therapeutic vaccines to eliminate HPV-infected and malignant cells holds significant value. In this study, we introduced a lipid nanoparticle encapsulated mRNA vaccine expressing tHA-mE7-mE6. Mutations were introduced into E6 and E7 of HPV to eliminate their tumourigenicity. A truncated influenza haemagglutinin protein (tHA), which binds to the CD209 receptor on the surface of dendritic cells (DCs), was fused with mE7-mE6 in order to allow efficient uptake of antigen by antigen presenting cells. The tHA-mE7-mE6 (mRNA) showed higher therapeutic efficacy than mE7-mE6 (mRNA) in an E6 and E7tumour model. The treatment resulted in complete tumour regression and prevented tumour formation. Strong CD8T-cell immune response was induced, contributing to preventing and curing of E6 and E7tumour. Antigen-specific CD8T were found in spleens, peripheral blood and in tumours. In addition, the tumour infiltration of DC and NK cells were increased post therapy. In conclusion, this study described a therapeutic mRNA vaccine inducing strong anti-tumour immunity in peripheral and in tumour microenvironment, holding promising potential to treat HPV-induced cancer and to prevent cancer recurrence. + + + +

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Preventing and Treating HPV-Related Cancer with an mRNA Vaccine That Targets Immune Cells

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