Preclinical development of peptide vaccination combined with oncolytic MG1-E6E7 for HPV-associated cancer

Area of Science:

• Oncolytic virology
• Immunotherapy
• Cancer vaccines

Background:

• Human papilloma virus (HPV)-associated cancers pose a global health challenge.
• Current therapeutic vaccines are ineffective against advanced HPV-driven diseases.
• Oncolytic viruses offer a novel approach to target HPV-positive cancer cells.

Purpose of the Study:

• To develop and evaluate synthetic long peptide (SLP) vaccines targeting HPV16 and HPV18 antigens.
• To assess the efficacy of combining SLP vaccines with an oncolytic Maraba virus (MG1-E6E7).
• To investigate the induction of anti-tumor immune responses and therapeutic outcomes in preclinical models.

Main Methods:

• Epitope mapping of mice vaccinated with MG1-E6E7 to design HPV-specific SLPs.
• Vaccination of mice with rationally designed SLPs and assessment of CD8+ T cell responses.
• Combination therapy using SLP vaccines and MG1-E6E7 in mice with established HPV-positive tumors.
• Evaluation of tumor clearance, survival, and long-term immunity upon tumor cell challenge.

Main Results:

• SLP vaccines induced specific CD8+ T cell responses against HPV antigens.
• Boosting with MG1-E6E7 significantly enhanced the magnitude and functionality of T cell responses.
• Combination therapy led to complete tumor clearance in 60% of mice with large tumors.
• Treated mice exhibited complete protection against long-term tumor re-challenge.

Conclusions:

• Rationally designed SLP vaccines combined with the oncolytic virus MG1-E6E7 are effective against advanced HPV-positive neoplasia.
• This combination strategy induces multi-functional CD8+ T cells and provides durable anti-tumor immunity.
• The findings suggest a promising therapeutic approach for treating advanced HPV-associated cancers.