The Antitumor Effect of a Non-transforming E7 Protein Combined with a TLR7 Agonist

Area of Science:

• Immunology
• Oncology
• Vaccinology

Background:

• Therapeutic vaccines for human papillomavirus (HPV)-induced cervical cancers face challenges in eliciting robust and sustained immune responses.
• The E7 protein is a key target for HPV vaccines, but its transforming properties can complicate vaccine development.

Purpose of the Study:

• To evaluate the vaccine potential of a modified HPV16 E7 protein (E7GGG) with eliminated transforming properties but retained antigenicity, in combination with Aldara (topical imiquimod) adjuvant.
• To assess the ability of HPV16-E7GGG and Aldara to induce humoral and cellular immune responses and inhibit tumor growth in a TC-1 mouse model.

Main Methods:

• Recombinant HPV16-E7GGG and wild-type E7 proteins were expressed and purified.
• Proteins were combined with Aldara adjuvant and administered to C57BL mice.
• Immune responses, including IgG, IL-4, IL-17, IFN-γ, and CTL activity, were measured. Tumor growth was monitored in the TC-1 mouse model.

Main Results:

• The HPV16-E7GGG antigen combined with Aldara adjuvant successfully induced significant humoral and cellular immune responses.
• Immune responses were characterized by a T helper 1 (TH1)-mediated pathway, indicated by elevated IL-17 and IFN-γ levels.
• Significant inhibition of tumor growth was observed in the immunized groups compared to controls.

Conclusions:

• The recombinant HPV16-E7GGG protein in combination with Aldara adjuvant demonstrates potential as a therapeutic vaccine candidate against HPV-induced cancers.
• The vaccine strategy elicits a TH1-biased immune response, crucial for effective anti-tumor immunity.
• Further investigation is warranted to explore its clinical applicability for cervical cancer treatment.